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1.
J Mol Graph Model ; 77: 232-239, 2017 10.
Article in English | MEDLINE | ID: mdl-28898788

ABSTRACT

Many species of bacteria involved in degradation of n-alkanes have an important constitutional metabolic enzyme, the alkane hydroxylase called AlkB, specialized in the conversion of hydrocarbons molecules that can be used as carbon and/or energy source. This enzyme plays an important role in the microbial degradation of oil, chlorinated hydrocarbons, fuel additives, and many other compounds. A number of these enzymes has been biochemically characterized in detail because the potential of alkane hydroxylases to catalyse high added-value reactions is widely recognized. Nevertheless, the industrial and process bioremediation application of them is restricted, owing to their complex biochemistry, challenging process requirements, and the limited number of their three-dimensional structures. Furthermore, AlkB has great potential as biocatalysts for selective transformation of a wide range of chemically inert unreactive alkanes into reactive chemical precursors that can be used as tools for bioremediation and bioprocesses. Aiming to understand the possible ways the AlkB enzyme Pseudomonas putida P1 interacts with octane, octanol and 1-octyne, we consider its suitable biochemical structure taking into account a 3-D homology modelling. Besides, by using a quantum chemistry computational model based on the density functional theory (DFT), we determine possible protein-substrate interaction regions measured by means of its binding energy simulated throughout the Molecular Fractionation with Conjugated Caps (MFCC) approach.


Subject(s)
Biodegradation, Environmental , Cytochrome P-450 CYP4A/chemistry , Pseudomonas putida/enzymology , Alkanes/chemistry , Models, Molecular , Octanes/chemistry , Quantum Theory
2.
Neuroscience ; 252: 337-45, 2013 Nov 12.
Article in English | MEDLINE | ID: mdl-23962648

ABSTRACT

Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 µg/µl) or N-methyl-d-aspartic acid (NMDA; 2 µg/µl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 µg/µl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 µg/µl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder.


Subject(s)
Dopamine/metabolism , Nucleus Accumbens/physiology , Receptors, Ionotropic Glutamate/physiology , Rhombencephalon/physiology , Synaptic Transmission/physiology , Ventral Tegmental Area/physiology , Animals , Electrophysiological Phenomena , Male , Microelectrodes , Rats , Rats, Wistar
3.
Genes Brain Behav ; 9(2): 129-59, 2010 Mar 01.
Article in English | MEDLINE | ID: mdl-19958391

ABSTRACT

Genetic reference populations, particularly the BXD recombinant inbred (BXD RI) strains derived from C57BL/6J and DBA/2J mice, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and covariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict the occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic coregulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium (TMGC) have obtained phenotype data from over 250 measures related to multiple behavioral assays across several batteries: response to, and withdrawal from cocaine, 3,4-methylenedioxymethamphetamine; "ecstasy" (MDMA), morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity and sleep/wake cycles. All traits have been measured in both sexes in approximately 70 strains of the recently expanded panel of BXD RI strains. Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent (N = 37) BXD RI lines was performed. Primary data are publicly available for heritability, sex difference and genetic analyses using the MouseTrack database, and are also available in GeneNetwork.org for quantitative trait locus (QTL) detection and genetic analysis of gene expression. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits.


Subject(s)
Recombination, Genetic , Alcohol Drinking/genetics , Animals , Behavior, Animal , Body Weight , Cocaine-Related Disorders/genetics , Habituation, Psychophysiologic/genetics , Handling, Psychological , Housing, Animal , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Morphine Dependence/genetics , Organ Size , Phenotype , RNA, Messenger/genetics , Substance-Related Disorders/genetics
4.
J Hum Hypertens ; 22(5): 320-8, 2008 May.
Article in English | MEDLINE | ID: mdl-18273040

ABSTRACT

Chronic dynamic (aerobic) exercise decreases central arterial stiffness, whereas chronic resistance exercise evokes the opposite effect. Nevertheless, there is little information available on the effects of acute bouts of exercise. Also, there is limited data showing an increase of central arterial stiffness during acute mental stress. This study aimed to determine the effect of acute mental and physical (static and dynamic exercise) stress on indices of central arterial stiffness. Fifteen young healthy volunteers were studied. The following paradigms were performed: (1) 2 min of mental arithmetic, (2) short bouts (20 s) of static handgrip at 20 and 70% of maximal voluntary contraction (MVC), (3) fatiguing handgrip at 40% MVC and (4) incremental dynamic knee extensor exercise. Central aortic waveforms were assessed using SphygmoCor software. As compared to baseline, pulse wave transit time decreased significantly for all four interventions indicating that central arterial stiffness increased. During fatiguing handgrip there was a fall in the ratio of peripheral to central pulse pressure from 1.69+/-0.02 at baseline to 1.56+/-0.05 (P<0.05). In the knee extensor protocol a non-significant trend for the opposite effect was noted. The augmentation index increased significantly during the arithmetic, short static and fatiguing handgrip protocols, whereas there was no change in the knee extensor protocol. We conclude that (1) during all types of acute stress tested in this study (including dynamic exercise) estimated central stiffness increased, (2) during static exercise the workload posed on the left ventricle (expressed as change in central pulse pressure) is relatively higher than that posed during dynamic exercise (given the same pulse pressure change in the periphery).


Subject(s)
Exercise/physiology , Hemodynamics/physiology , Stress, Psychological/physiopathology , Adult , Analysis of Variance , Blood Pressure/physiology , Elasticity , Female , Hand Strength , Heart Rate/physiology , Humans , Male , Muscle Fatigue/physiology , Vascular Resistance/physiology
5.
J Antimicrob Chemother ; 57(2): 273-8, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16344287

ABSTRACT

OBJECTIVES: Trichomonas vaginalis is the causative agent of trichomoniasis, a sexually transmitted disease with worldwide significance. Trichomoniasis can be treated with metronidazole; however, resistant strains of T. vaginalis have been isolated and there is a lack of useful alternative drugs. The aim of the present study was to examine the activity of hexadecylphosphocholine (HePC; miltefosine), a membrane-active alkylphospholipid, that is licensed as an antileishmanial agent against T. vaginalis. METHODS: The efficacy of HePC after 30 min, 1 h, 16 h and 24 h against four different T. vaginalis strains (with varying resistance to metronidazole) was evaluated. RESULTS: It was shown that all isolates, including the metronidazole-resistant strains, were susceptible to HePC, with EC50s of between 8 and 40 microM and EC90s of between 8 and 80 microM depending on time and on the medium used for the experiments. Treatment of trichomonads with HePC resulted in rounding up and, at concentrations of >or=40 microM, in subsequent total lysis of the organisms. CONCLUSIONS: HePC may be a promising new candidate for the treatment of trichomoniasis.


Subject(s)
Antifungal Agents/pharmacology , Metronidazole/pharmacology , Phosphorylcholine/analogs & derivatives , Trichomonas vaginalis/drug effects , Animals , DNA, Fungal/genetics , Drug Resistance, Fungal , Microbial Sensitivity Tests , Microscopy, Phase-Contrast , Phosphorylcholine/pharmacology , Species Specificity , Trichomonas vaginalis/genetics
6.
Neuroscience ; 136(2): 531-8, 2005.
Article in English | MEDLINE | ID: mdl-16216430

ABSTRACT

Midbrain dopamine neurons are critical in mediating the rewarding effects of opiates in dependent rats, as well as modulating some manifestations of opiate withdrawal. Morphine is known to excite dopamine neurons and thereby facilitate forebrain dopamine transmission through inhibition of GABA neurons. Cholinergic neurons in the mesopontine laterodorsal and pedunculopontine tegmental nuclei provide the principal source of excitatory cholinergic input to ventral tegmental area and substantia nigra pars compacta dopamine-containing neurons, via actions on midbrain muscarinic and nicotinic acetylcholine receptors. The present study hypothesized that a reduction in tonic cholinergic input via blockade of midbrain muscarinic receptors would reduce the pharmacological effects of morphine on forebrain dopamine release. Using in vivo chronoamperometry, alterations in morphine-evoked dopamine efflux were monitored at stearate-graphite paste electrodes implanted unilaterally in the nucleus accumbens and striatum of urethane (1.5 g/kg) anesthetized rats, following the pharmacological inhibition of ventral tegmental area/substantia nigra pars compacta muscarinic receptors. The facilitatory effects of morphine (2.0 mg/kg, i.v.) on accumbens and striatal dopamine efflux were markedly reduced by prior infusion of the non-selective muscarinic receptor antagonist scopolamine (200 microg/microl) into the ventral tegmental area or substantia nigra pars compacta, respectively. These findings demonstrate that decreased activation of midbrain muscarinic receptors attenuates the excitatory effects of morphine on mesoaccumbens and nigrostriatal dopaminergic transmission.


Subject(s)
Mesencephalon/physiology , Morphine/pharmacology , Narcotics/pharmacology , Neostriatum/metabolism , Nucleus Accumbens/metabolism , Receptors, Muscarinic/physiology , Animals , Electrochemistry , Electrodes , Injections, Intravenous , Male , Muscarinic Antagonists/pharmacology , Neostriatum/drug effects , Nucleus Accumbens/drug effects , Rats , Rats, Wistar , Scopolamine/pharmacology , Stereotaxic Techniques , Substantia Nigra/drug effects , Substantia Nigra/metabolism , Synaptic Transmission/drug effects , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/metabolism
7.
Neuroscience ; 125(2): 349-58, 2004.
Article in English | MEDLINE | ID: mdl-15062978

ABSTRACT

The pedunculopontine tegmental nucleus (PPTg) has long been suggested to have a role in reward-related behaviour, and there is particular interest in its possible role in drug reward systems. Previous work found increased i.v. self-administration (IVSA) of d-amphetamine following PPTg lesions when training had included both operant pre-training and priming injections. The present study examined the effect of excitotoxin lesions of the PPTg on d-amphetamine IVSA under three training conditions. Naive: no previous experience of d-amphetamine or operant responding. Pre-trained: given operant training with food before lesion surgery took place. Primed: given single non-contingent d-amphetamine infusion (0.1 mg/0.l ml) at the start of each session. Rats in all conditions were given either ibotenate or phosphate buffer control lesions of the PPTg before d-amphetamine (0.1 mg/0.1 ml infusion) IVSA training took place. Rats received eight sessions of training under a fixed ratio (FR2) schedule of d-amphetamine IVSA, followed by four sessions under a progressive ratio (PR5) schedule. In the naive condition, PPTg-lesioned rats were attenuated in their responding under FR2, and took significantly fewer infusions under PR5 than the control group. Under FR2 in the pre-trained condition, there was no difference between PPTg excitotoxin and control lesioned rats; however, PPTg-lesioned rats took significantly fewer infusions under the PR5 schedule. In the primed condition, there were no differences between PPTg-lesioned and control rats under either FR2 or PR5 schedules. These data demonstrate that operant training prior to PPTg lesion surgery corrects some, but not all, of the deficits seen in the naive condition. PPTg-lesioned rats in both naive and pre-trained conditions showed reduced responding for d-amphetamine under a PR5 schedule. These deficits are overcome by priming with d-amphetamine. We suggest that alterations in striatal dopamine activity following PPTg lesions underlie these effects.


Subject(s)
Central Nervous System Stimulants/administration & dosage , Dextroamphetamine/administration & dosage , Pedunculopontine Tegmental Nucleus/drug effects , Analysis of Variance , Animals , Behavior, Animal , Conditioning, Operant/drug effects , Drug Administration Schedule , Excitatory Amino Acid Agonists , Food , Ibotenic Acid , Male , NADP , Pedunculopontine Tegmental Nucleus/injuries , Pedunculopontine Tegmental Nucleus/physiology , Rats , Reinforcement Schedule , Reinforcement, Psychology , Self Administration/methods
8.
Genet. mol. res. (Online) ; 3(1): 167-180, Mar. 2004.
Article in English | LILACS | ID: lil-417575

ABSTRACT

Chromobacterium violaceum is a Gram-negative beta-proteobacterium that inhabits a variety of ecosystems in tropical and subtropical regions, including the water and banks of the Negro River in the Brazilian Amazon. This bacterium has been the subject of extensive study over the last three decades, due to its biotechnological properties, including the characteristic violacein pigment, which has antimicrobial and anti-tumoral activities. C. violaceum promotes the solubilization of gold in a mercury-free process, and has been used in the synthesis of homopolyesters suitable for the production of biodegradable polymers. The complete genome sequence of this organism has been completed by the Brazilian National Genome Project Consortium. The aim of our group was to study the DNA repair genes in this organism, due to their importance in the maintenance of genomic integrity. We identified DNA repair genes involved in different pathways in C. violaceum through a similarity search against known sequences deposited in databases. The phylogenetic analyses were done using programs of the PHILYP package. This analysis revealed various metabolic pathways, including photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, recombinational repair, and the SOS system. The similarity between the C. violaceum sequences and those of Neisserie miningitidis and Ralstonia solanacearum was greater than that between the C. violaceum and Escherichia coli sequences. The peculiarities found in the C. violaceum genome were the absence of LexA, some horizontal transfer events and a large number of repair genes involved with alkyl and oxidative DNA damage


Subject(s)
Chromobacterium/genetics , Bacterial Proteins/genetics , DNA Repair/genetics , Sequence Homology , Databases, Genetic , Phylogeny , Base Pair Mismatch/genetics , Recombination, Genetic , SOS Response, Genetics/genetics
9.
Neuroscience ; 114(4): 817-23, 2002.
Article in English | MEDLINE | ID: mdl-12379238

ABSTRACT

Cholinergic and glutamatergic projections from the laterodorsal tegmental nucleus (LDT) in the rat pons excite midbrain dopamine cells to directly modulate forebrain dopamine transmission. We show that LDT-lesioned rats express higher intensity stereotypy (including orofacial movements), and higher levels of accumbal dopamine release in response to d-amphetamine (1.5 mg/kg), as compared to sham-operated rats. In contrast, LDT-lesioned rats showed decreased stereotypy and attenuated accumbal dopamine efflux as compared to sham animals, in response to morphine (2.0 mg/kg). These results suggest that the LDT plays a critical role in mediating motoric and neurochemical effects of diverse drugs of abuse, and that the pharmacology of the drug may critically determine whether its efficacy will be enhanced or attenuated by alterations in LDT activity. We conclude that the LDT has functional connections with the nigrostriatal dopamine system to affect drug-evoked stereotypy, which has implications for motoric disorders that are characterized by nigrostriatal dysfunction.


Subject(s)
Analgesics, Opioid/pharmacology , Dextroamphetamine/pharmacology , Dopamine Agents/pharmacology , Dopamine/metabolism , Morphine/pharmacology , Pons/drug effects , Animals , Behavior, Animal/physiology , Denervation , Locomotion/physiology , Male , Neurotoxins/pharmacology , Pons/physiology , Rats , Rats, Wistar , Stereotyped Behavior/physiology , Stimulation, Chemical
10.
Neuroscience ; 111(2): 351-62, 2002.
Article in English | MEDLINE | ID: mdl-11983320

ABSTRACT

Cholinergic and glutamatergic cells in the pedunculopontine tegmental nucleus are a principal source of excitatory input to midbrain dopamine neurons projecting to the striatum. Disruption of these brainstem inputs has been shown to respectively enhance and reduce psychostimulant and opiate self-administration in rats. In the present study, d-amphetamine- and morphine-induced behaviors and dorsal striatal dopamine efflux, measured using in vivo chronoamperometry, were investigated 21 days after bilateral excitotoxic (ibotenate) lesions of the pedunculopontine in rats. Compared to sham-operated controls, pedunculopontine lesions enhanced stereotyped behaviors induced by a challenge injection of d-amphetamine (1.5 mg/kg, i.p.) to an extent that markedly interfered with the expression of locomotor behavior. A significant augmentation in striatal dopamine efflux was also observed in these lesioned animals under urethane anesthesia in response to a similar challenge injection of d-amphetamine (1.5 mg/kg, i.v.) 2 days following these behavioral observations. In direct contrast, pedunculopontine lesions in a separate group of rats significantly attenuated morphine-induced (2 mg/kg, i.p.) stereotyped activity, although no significant differences were observed in locomotion compared to sham-operated animals. Under urethane anesthesia, these lesions attenuated striatal dopamine efflux evoked by a similar challenge injection of morphine (2 mg/kg, i.v.). These findings indicate that the pedunculopontine differentially mediates the pharmacological actions of two diverse drugs of abuse on striatal dopamine neurotransmission and resultant behaviors. These results also imply that the pedunculopontine tegmental nucleus may serve as a major striatal-motor interface in the processing of salient environmental stimuli, and their incentive rewarding impact on dopamine-mediated behavioral responses.


Subject(s)
Behavior, Animal/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dextroamphetamine/pharmacology , Dopamine/metabolism , Excitatory Amino Acid Agonists/pharmacology , Ibotenic Acid/pharmacology , Morphine/pharmacology , Neurotoxins/pharmacology , Pons/drug effects , Pons/physiology , Animals , Male , Motor Activity/drug effects , Motor Activity/physiology , Rats , Rats, Wistar , Stereotyped Behavior/physiology
11.
J Neurosci ; 21(16): 6370-6, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11487660

ABSTRACT

Interactions between the basolateral amygdala (BLA) and the nucleus accumbens (NAc) mediate reward-related processes that are modulated by mesoaccumbens dopamine (DA) transmission. The present in vivo electrophysiological study assessed: (1) changes in the firing probability of submaximal BLA-evoked single neuronal firing activity in the NAc after tetanic stimulation of the BLA, and (2) the functional roles of DA and NMDA receptors in these processes. Tetanic stimulation of the BLA potentiated BLA-evoked firing activity of NAc neurons for a short duration ( approximately 25 min). This short-term potentiation was associated with an increase in DA oxidation currents that was monitored with chronoamperometry. Systemic or iontophoretic application before BLA tetanus of the D(1) receptor antagonist SCH23390, but not the D(2) receptor antagonist sulpiride, abolished the potentiation of BLA-evoked NAc activity, whereas administration of SCH23390 3 min after tetanus had no effect. However, systemic administration of the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), either before or after BLA tetanus, abolished the potentiation of BLA-evoked firing of NAc neurons. These data suggest that higher-frequency activity in BLA efferents can autoregulate their excitatory influence over neural activity of NAc neurons by facilitating the release of DA and activating both DA D(1) and NMDA receptors. This may represent a cellular mechanism that facilitates approach behaviors directed toward reward-related stimuli that are mediated by BLA-NAc circuitries.


Subject(s)
Amygdala/metabolism , Neurons/metabolism , Nucleus Accumbens/metabolism , Receptors, Dopamine D1/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Dopamine/metabolism , Dopamine Antagonists/pharmacology , Electric Stimulation , Electrochemistry , Electrodes, Implanted , Excitatory Amino Acid Antagonists/pharmacology , Iontophoresis , Male , Nucleus Accumbens/cytology , Rats , Rats, Long-Evans , Receptors, Dopamine D1/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Reward
12.
Life Sci ; 68(22-23): 2449-56, 2001 Apr 27.
Article in English | MEDLINE | ID: mdl-11392612

ABSTRACT

Mesopontine cholinergic neurons (Ch5 and Ch6 cell groups) activate the cerebral cortex via thalamic projections, and activate locomotion and reward via dopamine neurons in the substantia nigra and ventral tegmental area (VTA). Nicotinic receptors in VTA activate dopamine neurons quickly, and are needed for the stimulant and rewarding effects of nicotine in rats. Muscarinic receptors in VTA activate dopamine neurons slowly, and are needed for the rewarding effects of hypothalamic stimulation, but do not increase locomotion. Antisense oligonucleotides targetting M5 mRNA, when infused into the VTA, inhibited M5 receptor binding and rewarding hypothalamic stimulation. Mutant mice with truncated M5 muscarinic receptor genes drank more water than wild-type controls. Spontaneous locomotion and locomotor responses to amphetamine and scopolamine were unchanged. Electrical stimulation near Ch6 induced dopamine release in the nucleus accumbens in two phases, an early phase (0-2 min after stimulation) dependent on nicotinic and gluatamatergic receptors in VTA, and a late phase (8-50 min after stimulation) dependent on muscarinic receptors in VTA. The late phase was lost in M5 mutant mice, while the early phase was unchanged. M5 muscarinic receptors bind slowly to muscarinic ligands, and appear to mediate slow secretions.


Subject(s)
Corpus Striatum/physiology , Dopamine/metabolism , Neurons/metabolism , Receptors, Muscarinic/metabolism , Acetylcholine/metabolism , Acetylcholine/pharmacology , Animals , Corpus Striatum/cytology , Corpus Striatum/drug effects , Dopamine/pharmacology , Electric Stimulation , Humans , Hypothalamus/cytology , Hypothalamus/physiology , Neurons/drug effects , Receptor, Muscarinic M5 , Receptors, Muscarinic/genetics , Receptors, Nicotinic/metabolism , Reward
13.
J Neurosci ; 21(8): 2851-60, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11306637

ABSTRACT

Inputs from multiple sites in the telencephalon, including the hippocampus and basolateral amygdala (BLA), converge on neurons in the nucleus accumbens (NAc), and dopamine (DA) is believed to play an essential role in the amplification and gating of these different limbic inputs. The present study used extracellular single-unit recordings of NAc neurons in combination with chronoamperometric sampling of mesoaccumbens DA efflux to assess the importance of DA in the integration of different limbic inputs to the NAc. Tetanic stimulation of the fimbria potentiated hippocampal-evoked firing activity of NAc neurons and increased DA extracellular levels. Systemic administration of the D(1) receptor antagonist SCH23390 or the NMDA receptor antagonist CPP abolished the potentiation of hippocampal-evoked activity and produced a D(2) receptor-mediated suppression of evoked firing. In neurons that received converging input from the hippocampus and BLA, fimbria tetanus potentiated hippocampal-evoked firing activity and suppressed BLA-evoked activity in the same neurons. Both D(1) and NMDA receptors participated in the potentiation of fimbria-evoked activity, whereas the suppression of BLA-evoked activity was blocked by either D(1) receptor antagonism with SCH23390 or the adenosine A(1) antagonist 8-cyclopentyl-1,2-dimethylxanthine. Coincidental tetanus of both the fimbria and BLA resulted in potentiation of both inputs, indicating that DA and adenosine-mediated suppression of BLA-evoked firing was activity-dependent. These data suggest that increases in mesoaccumbens DA efflux by hippocampal afferents to the NAc play a critical role in an input selection mechanism, which can ensure preferential responding to the information conveyed from the hippocampus to the ventral striatum.


Subject(s)
Amygdala/physiology , Dopamine/metabolism , Hippocampus/physiology , Neurons/metabolism , Nucleus Accumbens/metabolism , Action Potentials/drug effects , Action Potentials/physiology , Animals , Dopamine/pharmacology , Dopamine Antagonists/pharmacology , Dose-Response Relationship, Drug , Electric Stimulation , Excitatory Amino Acid Antagonists/pharmacology , Fornix, Brain/physiology , Glutamic Acid/metabolism , Male , Nerve Net/metabolism , Neurons/drug effects , Nucleus Accumbens/cytology , Nucleus Accumbens/drug effects , Purinergic P1 Receptor Antagonists , Rats , Rats, Long-Evans , Reaction Time/drug effects , Reaction Time/physiology , Receptors, Dopamine D1/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
14.
Behav Brain Res ; 120(2): 147-58, 2001 May.
Article in English | MEDLINE | ID: mdl-11182163

ABSTRACT

The present experiment employed chronoamperometry with stearate-graphite paste electrodes to monitor dopamine efflux in the nucleus accumbens during extinction and subsequent reinstatement of bar-pressing for a conditioned stimulus (CS) following presentation of a CS or following a systemic injection of d-amphetamine. Rats self-administered d-amphetamine (0.25 mg/kg per infusion) for 3 h a day on 6 consecutive days. Each infusion was paired with a flashing light CS. On the 7th day, rats self-administered d-amphetamine for 1 h, followed by 10 h of extinction. Presentation of the CS 2 days following extinction induced small and transient increases in responding for the CS, with no significant associated increases in DA efflux. Lower rates of responding were observed in rats that had received random presentations of the CS during d-amphetamine self-administration, and in an experimentally-naïve control group. A subsequent systemic injection of d-amphetamine increased dopamine efflux in the nucleus accumbens in all groups and was most effective in reinstating bar-pressing in the CS-d-amphetamine paired group. This is consistent with the hypothesis that exposure to psychostimulant drugs, and a drug-paired CS, can reinstate drug-seeking behavior. Together, these findings suggest that enhanced DA efflux may contribute to the reinstatement of drug-seeking behavior induced by the single administration of a psychostimulant drug, but not transient reinstatement induced by presentation of a drug-paired CS alone following extinction.


Subject(s)
Conditioning, Operant/physiology , Dextroamphetamine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Dopamine/metabolism , Extinction, Psychological/physiology , Substance-Related Disorders/psychology , Animals , Conditioning, Operant/drug effects , Electrochemistry , Electrodes , Male , Microdialysis , Nucleus Accumbens/anatomy & histology , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Oxidation-Reduction , Rats , Rats, Long-Evans
15.
Eur J Neurosci ; 12(10): 3596-604, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11029630

ABSTRACT

Cholinergic and glutamatergic neurons in the laterodorsal tegmentum (LDT) and neighbouring mesopontine nuclei are thought to influence mesolimbic dopaminergic neuronal activity involved in goal-directed behaviours. We measured the changes in dopamine oxidation current (corresponding with dopamine efflux) in the nucleus accumbens (NAc) in response to electrical stimulation of the LDT using in vivo chronoamperometry in urethane-anaesthetized rats. LDT stimulation (35 Hz pulse trains for 60 s, 1 s intertrain interval) evoked a three-component change in dopamine efflux in the NAc: (i) an initial stimulation time-locked increase in the dopamine signal above baseline, followed by (ii) an immediate decrease below baseline, and thereafter by (iii) a prolonged increase in the dopamine signal above baseline. Intra-VTA infusion of the nicotinic receptor antagonist mecamylamine (5 microg/0.5 microL) or the ionotropic glutamate receptor antagonist kynurenate (10 microg/microL) attenuated the first LDT-elicited component. The second suppressive component was abolished by intra-LDT infusions of either the nonselective or the M2-selective muscarinic receptor antagonists scopolamine (100 microg/microL) and methoctramine (50 microg/microL), respectively. In contrast, intra-VTA infusions of scopolamine (200 microg/microL) resulted in a selective attenuation of the third facilitatory component, whereas both second and third components were abolished by systemic injections of scopolamine (5 mg/kg). These results suggest that the initial increase, subsequent decrease, and final prolonged increase in extracellular dopamine levels in the NAc are selectively mediated by LDT-elicited activation of (i) nicotinic and glutamatergic receptors in the VTA, (ii) muscarinic M2 autoreceptors on LDT cell bodies, and (iii) muscarinic receptors in the VTA, respectively.


Subject(s)
Dopamine/metabolism , Neural Pathways/metabolism , Nucleus Accumbens/metabolism , Pons/metabolism , Receptors, Cholinergic/metabolism , Receptors, Glutamate/metabolism , Ventral Tegmental Area/metabolism , Animals , Cholinergic Fibers/metabolism , Cholinergic Fibers/ultrastructure , Diamines/pharmacology , Electric Stimulation , Kynurenic Acid/pharmacology , Male , Mecamylamine/pharmacology , Neural Pathways/cytology , Neural Pathways/drug effects , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Nucleus Accumbens/cytology , Parasympatholytics/pharmacology , Pons/cytology , Pons/drug effects , Rats , Rats, Wistar , Receptors, Cholinergic/drug effects , Receptors, Glutamate/drug effects , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/metabolism , Receptors, Nicotinic/drug effects , Receptors, Nicotinic/metabolism , Scopolamine/pharmacology , Stereotaxic Techniques , Ventral Tegmental Area/cytology , Ventral Tegmental Area/drug effects
16.
Nurs Case Manag ; 5(1): 32-6, 2000.
Article in English | MEDLINE | ID: mdl-10855156

ABSTRACT

Longitudinal case management is an intervention delivered by professional nurses that involves following patients from the inpatient to the outpatient arena. The hands-on process of day-to-day case management of elderly persons with heart failure is presented. The issues associated with delivering this intervention to this patient population are examined, and implications for refining the case management process are discussed.


Subject(s)
Case Management/organization & administration , Heart Failure/nursing , Long-Term Care/organization & administration , Patient Care Team/organization & administration , Aged , Continuity of Patient Care , Female , Heart Failure/economics , Heart Failure/psychology , Humans , Long-Term Care/psychology , Male , Models, Nursing , Nursing Evaluation Research , Patient Discharge , Patient Education as Topic/organization & administration , Program Evaluation , Quality of Life
17.
FEMS Microbiol Lett ; 183(1): 23-9, 2000 Feb 01.
Article in English | MEDLINE | ID: mdl-10650197

ABSTRACT

Disruption of an open reading frame (ORF) of 840 bp (280 amino acids; ORF280) in an Azospirillum brasilense Tn5 mutant resulted in a pleiotrophic phenotype. Besides an enhanced N(2)-fixing capacity and altered expression pattern of a nifH-gusA fusion, growth on the charged polar amino acids glutamate and arginine was severely affected. ORF280, similar to previously identified ORFs present in Bradyrhizobium japonicum (ORF277), Paracoccus denitrificans (ORF278) and Rhodobacter capsulatus (ORF277), exhibits in its C-terminus a significant similarity with the recently defined family of universal stress proteins.


Subject(s)
Azospirillum brasilense/genetics , DNA Transposable Elements , Nitrogen Fixation/genetics , Nitrogenase/genetics , Open Reading Frames/genetics , Oxidoreductases , Amino Acid Sequence , Azospirillum brasilense/metabolism , Cloning, Molecular , DNA, Bacterial/analysis , Glucuronidase/metabolism , Molecular Sequence Data , Mutation , Nitrogen Fixation/physiology , Nitrogenase/metabolism , Physical Chromosome Mapping , Recombinant Fusion Proteins/metabolism , Sequence Analysis, DNA
18.
Holist Nurs Pract ; 13(2): 61-5, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10196904

ABSTRACT

It is estimated that 3 million persons in the United States have congestive heart failure. This diagnosis accounts for more than 5% of total health expenditures. A method to decrease the costs of health care was initiated through the partners-in-care model of collaborative practice. A research study exploring the use of nurse case managers in collaboration with cardiologists and primary care physicians is being conducted with persons older than 65 years. This care encompasses both inpatient and outpatient care. The intervention comprises nurse visits in the hospital and in the home as well as telephone support for 6 months after the index hospitalization. The outcomes of quality of life, functional status, mortality, morbidity, and costs are being examined. Collaborative health care partnerships may be an effective strategy to decrease health care costs and improve quality of life and functional status of older persons with congestive heart failure.


Subject(s)
Cardiology/organization & administration , Case Management/organization & administration , Cooperative Behavior , Family Practice/organization & administration , Heart Failure/therapy , Interprofessional Relations , Models, Organizational , Patient Care Team/organization & administration , Aged , Cost Control , Female , Humans , Male
19.
Eur J Neurosci ; 10(4): 1241-51, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9749778

ABSTRACT

Afferents from the basolateral amygdala and dopamine projections from the ventral tegmental area to the nucleus accumbens have both been implicated in reward-related processes. The present study used in vivo chronoamperometry with stearate-graphite paste electrodes in urethane-anaesthetized rats to determine how basolateral amygdala efferents to the nucleus accumbens synaptically regulate dopamine efflux. Repetitive-pulse (20 Hz for 10 s) electrical stimulation of the basolateral amygdala evoked a complex pattern of changes in monitored dopamine oxidation currents in the nucleus accumbens related to dopamine efflux. These changes were characterized by an initial increase that was time-locked to stimulation, a secondary decrease below baseline, followed by a prolonged increase in the dopamine signal above baseline. The effects of burst-patterned stimulation (100 Hz, 5 pulses/burst, 1-s interburst interval, 40 s) of the basolateral amygdala on the basal accumbens dopamine signal were similar to those evoked by 20 Hz stimulation, with the lack of a secondary suppressive component. Infusions of the ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid (APV) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the nucleus accumbens dose-dependently blocked or attenuated the initial and prolonged increases in the dopamine signal following 20 Hz or burst-patterned basolateral amygdala stimulation. Infusions of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine selectively blocked the intermediate suppressive effect of 20 Hz basolateral amygdala stimulation on dopamine oxidation currents. Blockade of glutamate receptors or inhibition of dopamine neuronal activity via infusions of either APV + DNQX, lidocaine or gamma-hydroxybutyric acid, respectively, into the ventral tegmental area did not effect the pattern of changes in the accumbens dopamine signal evoked by basolateral amygdala stimulation. These data suggest that the glutamatergic basolateral amygdala inputs to nucleus accumbens dopamine terminals synaptically facilitate or depress dopamine efflux, and these effects are independent of dopamine neuronal firing activity. Moreover, these results imply that changes in nucleus accumbens dopamine levels following presentation of reward-related stimuli may be mediated, in part, by the basolateral amygdala.


Subject(s)
Amygdala/physiology , Dopamine/metabolism , Nucleus Accumbens/metabolism , Receptors, Glutamate/physiology , Amygdala/drug effects , Anesthetics, Intravenous , Animals , Electric Stimulation , Electrochemistry , Evoked Potentials/drug effects , Evoked Potentials/physiology , Excitatory Amino Acid Antagonists/pharmacology , Male , Nucleus Accumbens/drug effects , Presynaptic Terminals/drug effects , Presynaptic Terminals/metabolism , Rats , Receptors, Glutamate/drug effects , Reward , Stereotaxic Techniques , Urethane
20.
Eur J Neurosci ; 10(3): 1121-7, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9753180

ABSTRACT

In vivo chronoamperometry was used to monitor changes in dopamine oxidation currents corresponding to dopamine efflux in the nucleus accumbens of rats after presentation of a conditioned light stimulus repeatedly paired with either yoked- or self-administered intravenous injections of the psychostimulant d-amphetamine. Daily conditioning trials began with a non-contingent drug injection, paired with a conditioned stimulus consisting of a 5 s flashing light and 30 s lights out, after which a house light was illuminated during the 3 h session, signalling drug availability. Each subsequent injection of d-amphetamine was paired with the conditioned stimulus. Electrochemical measures were taken on conditioning trials 4-7, and on each trial, intravenous d-amphetamine (0.25 mg/kg per injection) self-administration produced a significant maximal increase in mean dopamine oxidation currents of approximately 8 nA above baseline. Dopamine oxidation currents in rats receiving yoked d-amphetamine were approximately 5 nA above baseline by the fourth day of drug administration and reached approximately 8 nA on the seventh and final day of drug administration. On day 9 the first presentation of the vehicle injection and conditioned stimulus, in combination with illumination of the house lights, induced an immediate increase in nucleus accumbens dopamine oxidation currents in all rats that had previously received d-amphetamine. Subsequent presentations of the conditioned stimulus at 30 min intervals induced further increases in extracellular dopamine oxidation currents in both drug-treated groups. By the end of the 3 h session, both groups had similar maximal conditioned increases in dopamine oxidation currents of approximately 6 nA. These data are discussed with relation to the neurochemistry of drug craving.


Subject(s)
Dextroamphetamine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Dopamine/metabolism , Nucleus Accumbens/metabolism , Animals , Dextroamphetamine/administration & dosage , Dopamine Uptake Inhibitors/administration & dosage , Electrochemistry , Male , Nucleus Accumbens/anatomy & histology , Nucleus Accumbens/drug effects , Oxidation-Reduction , Photic Stimulation , Rats , Self Administration
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