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1.
Behav Brain Res ; 294: 215-23, 2015 Nov 01.
Article in English | MEDLINE | ID: mdl-26275926

ABSTRACT

In order to investigate the role of modus operandi in the changes of nucleus accumbens (NAc) dopamine (DA) transmission in sucrose reinforcement, extracellular DA was monitored by microdialysis in the NAc shell and core of rats trained on a fixed-ratio 1 schedule to respond for sucrose pellets by nose poking and lever pressing respectively. After training, rats were tested on three different sessions: sucrose reinforcement, extinction and passive sucrose presentation. In rats responding by nose poking dialysate DA increased in the shell but not in the core under reinforced as well as under extinction sessions. In contrast, in rats responding by lever pressing dialysate DA increased both in the accumbens shell and core under reinforced and extinction sessions. Response non-contingent sucrose presentation increased dialysate DA in the shell and core of rats trained to respond for sucrose by nose poking as well as in those trained by lever pressing. In rats trained to respond for sucrose by nose poking on a FR5 schedule dialysate DA also increased selectively in the NAc shell during reinforced responding and in both the shell and core under passive sucrose presentation. These findings, while provide an explanation for the discrepancies existing in the literature over the responsiveness of shell and core DA in rats responding for food, are consistent with the notion that NAc shell and core DA encode different aspects of reinforcement.


Subject(s)
Dopamine/metabolism , Forelimb/physiology , Motor Activity/physiology , Nose/physiology , Nucleus Accumbens/metabolism , Reinforcement, Psychology , Animals , Catheters, Indwelling , Dietary Sucrose/administration & dosage , Extinction, Psychological/physiology , Extracellular Space/metabolism , Male , Microdialysis , Rats, Sprague-Dawley
2.
Eur J Neurosci ; 41(6): 802-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25645148

ABSTRACT

This study investigated by microdialysis the role of response contingency and food-associated cues in the responsiveness of dopamine transmission in the nucleus accumbens shell and core to sucrose feeding. In naive rats, single-trial non-contingent presentation and feeding of sucrose pellets increased dialysate shell dopamine and induced full habituation of dopamine responsiveness to sucrose feeding 24 and 48 h later. In rats trained to respond for sucrose pellets on a fixed ratio 1 (FR1) schedule, dialysate dopamine increased in the shell but not in the core during active responding as well as under extinction in the presence of sucrose cues. In rats yoked to the operant rats, the presentation of sucrose cues also increased dialysate dopamine selectively in the shell. In contrast, non-contingent sucrose presentation and feeding in FR1-trained and in yoked rats increased dialysate dopamine to a similar extent in the shell and core. It is concluded that, whereas non-contingent sucrose feeding activated dopamine transmission in the shell and core, response-contingent feeding activated, without habituation, dopamine transmission selectively in the shell as a result of the action of sucrose conditioned cues. These observations are consistent with a critical role of conditioned cues acquired during training and differential activation of shell vs. core dopamine for response-contingent sucrose feeding.


Subject(s)
Conditioning, Operant/physiology , Cues , Dopamine/physiology , Nucleus Accumbens/physiology , Sucrose , Animals , Behavior, Animal/physiology , Dopamine/analysis , Extinction, Psychological/physiology , Male , Microdialysis , Nucleus Accumbens/chemistry , Rats , Rats, Sprague-Dawley , Reinforcement Schedule
3.
J Neuroendocrinol ; 25(11): 1196-208, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23795653

ABSTRACT

Tourette's syndrome (TS) is a neurodevelopmental disorder characterised by recurring motor and phonic tics. The pathogenesis of TS is considered to reflect dysregulations in the signalling of dopamine (DA) and other neurotransmitters, which lead to excitation/inhibition imbalances in cortico-striato-thalamocortical circuits. The causes of these deficits may reflect complex gene × environment × sex (G × E × S) interactions; indeed, the disorder is markedly predominant in males, with a male-to-female prevalence ratio of approximately 4 : 1. Converging lines of evidence point to neuroactive steroids as being likely molecular candidates to account for G × E × S interactions in TS. Building on these premises, our group has begun examining the possibility that alterations in the steroid biosynthetic process may be directly implicated in TS pathophysiology; in particular, our research has focused on 5α-reductase (5αR), the enzyme catalysing the key rate-limiting step in the synthesis of pregnane and androstane neurosteroids. In clinical and preclinical studies, we found that 5αR inhibitors exerted marked anti-DAergic and tic-suppressing properties, suggesting a central role for this enzyme in TS pathogenesis. Based on these data, we hypothesise that enhancements in 5αR activity in early developmental stages may lead to an inappropriate activation of the 'backdoor' pathway for androgen synthesis from adrenarche until the end of puberty. We predict that the ensuing imbalances in steroid homeostasis may impair the signalling of DA and other neurotransmitters, ultimately resulting in the facilitation of tics and other behavioural abnormalities in TS.


Subject(s)
Androgens , Cholestenone 5 alpha-Reductase/physiology , Neurotransmitter Agents , Tourette Syndrome/metabolism , Androgens/biosynthesis , Androgens/physiology , Cholestenone 5 alpha-Reductase/antagonists & inhibitors , Female , Gene-Environment Interaction , Humans , Male , Neurotransmitter Agents/biosynthesis , Neurotransmitter Agents/physiology , Sex Factors , Tourette Syndrome/etiology , Tourette Syndrome/genetics
4.
Neuropharmacology ; 65: 58-64, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22982249

ABSTRACT

The putative 5-HT6 receptor agonist ST1936 has been shown to increase extracellular dopamine (DA) in the n.accumbens (NAc) shell and in the medial prefrontal cortex (PFCX). These observations suggest that 5-HT6 receptors modulate DA transmission in mesolimbic and mesocortical terminal DA areas. To investigate the behavioral counterpart of this interaction we studied in rats 1) the ability of ST1936 to maintain i.v. self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement; 2) the effect of 5-HT6 receptor blockade on cocaine stimulated overflow of DA in dialysates from the PFCX and from the NAc shell and on cocaine i.v. self-administration. ST1936 was i.v. self-administered at unitary doses of 0.5-1 mg/kg on an FR1 and PR schedule of reinforcement, with breaking point of about 4. Pretreatment with the 5-HT6 antagonist SB271046 reduced by about 80% responding for ST1936. SB271046 also reduced cocaine-induced increase of dialysate DA in the NAc shell but not in the PFCX and impaired i.v. cocaine self-administration. These observations indicate that ST1936 behaves as a weak reinforcer and suggest that 5-HT6 receptors play a role in cocaine reinforcement via their facilitatory interaction with DA projections to the NAc shell. This novel 5-HT/DA interaction might provide the basis for a new pharmacotherapeutic strategy of cocaine addiction.


Subject(s)
Behavior, Addictive/metabolism , Cocaine/administration & dosage , Dopamine/metabolism , Receptors, Serotonin/metabolism , Reinforcement Schedule , Animals , Dopamine/physiology , Ethylamines/pharmacology , Indoles/pharmacology , Male , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Serotonin/physiology , Self Administration
5.
Neuropharmacology ; 60(4): 602-8, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21185318

ABSTRACT

The function of 5-HT6 receptors, one of the last additions to the large family of 5-HT receptors, is largely unknown due to the limited knowledge of their transduction mechanisms, lack of full centrally acting agonists and inconsistencies in the pharmacological and neurochemical effects of the antagonists. Recently, a new full agonist, ST1936, with nanomolar affinity for 5-HT6 receptors, has become available. Here we report the effect of ST1936 (5-10-20 mg/kg/ip) on dialysate DA, NA and 5-HT in the medial prefrontal cortex (PFCX) and in the shell and core of the nucleus accumbens (NAc). Systemic administration of ST1936 dose-dependently increased dialysate DA and NA in the NAc shell and PFCX and to a lesser extent in the NAc core; these effects were prevented by systemic administration of the two 5-HT6 receptor antagonists, SB271046 (10-20 mg/kg/ip) and SB399885 (5 mg/kg/ip). These properties of ST1936 suggest that 5-HT6 receptors control the activity of DA and NA neurons projecting to the NAc and to the PFCX.


Subject(s)
Ethylamines/pharmacology , Indoles/pharmacology , Nucleus Accumbens/drug effects , Prefrontal Cortex/drug effects , Receptors, Serotonin/metabolism , Serotonin Receptor Agonists/pharmacology , Analysis of Variance , Animals , Dopamine/metabolism , Dose-Response Relationship, Drug , Male , Microdialysis , Norepinephrine/metabolism , Nucleus Accumbens/metabolism , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley , Serotonin/metabolism , Serotonin Antagonists/pharmacology , Sulfonamides/pharmacology , Thiophenes/pharmacology
6.
J Neurochem ; 98(1): 113-21, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16805801

ABSTRACT

Parietal and occipital cortices, while densely innervated by noradrenalin 2 (NA) projections, possess a comparatively sparse dopamine 2 (DA) innervation, even sparser than the prefrontal cortex. We previously reported that reboxetine and desipramine, two selective norepinephrine transporter (NET) blockers, at doses that maximally increase DA in the prefrontal cortex, do not increase DA in the parietal and occipital cortices. In the present study, we performed a full dose-response study of the effect of systemic reboxetine and desipramine on DA and NA in dialysates from the parietal and occipital cortices. Seven doses of reboxetine (0.1, 0.25, 0.5, 1.0, 2.5, 5.0 and 10 mg/kg) and four doses of desipramine (0.25, 1.0, 2.5 and 5.0 mg/kg) were tested. Reboxetine and desipramine differentially affected dialysate DA as compared with NA. Reboxetine increased DA maximally by about 100% after doses of 0.25-0.5 mg/kg and showed a bell-shaped dose-response function in both areas; desipramine did not affect DA in the parietal cortex and increased it in the occipital cortex only at 2.5 mg/kg. NA was maximally increased by 275% by 0.5-2.5 mg/kg reboxetine and by about 300% by 5.0 mg/kg desipramine with a more linear dose-response curve. The mechanism of peculiar dose-response function of dialysate DA after reboxetine and desipramine was further investigated by testing the effect of drugs on dialysate DA and NA under alpha(2) receptor blockade. Under local perfusion of the occipital cortex with idazoxan, an otherwise ineffective dose of reboxetine and desipramine (5 mg/kg) became effective in raising extracellular DA. In contrast, the effect of reboxetine on NA was potentiated, while that of desipramine was not affected. These results suggest that, in the parietal and occipital cortices, extracellular NA, raised by NET blockade, exerts a preferential inhibitory influence on DA release by acting on local alpha(2) receptors, thus accounting for the bell-shaped feature of the dose-response function of drugs on dialysate DA in these areas.


Subject(s)
Dopamine/metabolism , Neural Inhibition/physiology , Norepinephrine/metabolism , Occipital Lobe/metabolism , Parietal Lobe/metabolism , Receptors, Adrenergic, alpha-2/physiology , Adrenergic Uptake Inhibitors/pharmacology , Analysis of Variance , Animals , Desipramine/pharmacology , Dialysis/methods , Dose-Response Relationship, Drug , Male , Morpholines/pharmacology , Neural Inhibition/drug effects , Occipital Lobe/cytology , Occipital Lobe/drug effects , Parietal Lobe/cytology , Parietal Lobe/drug effects , Rats , Rats, Sprague-Dawley , Reboxetine , Time Factors
7.
J Neurochem ; 93(2): 371-82, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15816860

ABSTRACT

The present study investigated the effects of two serotonin (5-HT) uptake inhibitors, citalopram and paroxetine, and of a non-selective noradrenaline (NA) and 5-HT uptake blocker, imipramine, on extracellular NA and dopamine (DA) in the prefrontal cortex (PfCX), parietal cortex (ParCX) and occipital cortex (OccCX). Citalopram, the most selective 5-HT uptake blocker, increased dialysate DA in the OccCX and ParCX but not in the PfCX and this effect was prevented in the OccCX by WAY-100635, an antagonist of serotonin-1A (5-HT(1A)) receptors, but not by dorsal noradrenergic bundle (DNAB) lesions that reduced to unmeasurable levels basal dialysate NA but did not affect dialysate DA. Paroxetine, a less selective 5-HT uptake inhibitor than citalopram, at the dose of 5 mg/kg, increased DA in the OccCX but not in the PfCX; however, at doses of 10 mg/kg, which increase PfCX NA, paroxetine increased DA also in this area. Imipramine increased dialysate DA and NA both in the PfCX and in the OccCX and this effect was abolished by DNAB lesions and was reduced but not abolished by WAY-100635. Administration of doses of reboxetine and citalopram that do not increase DA release in the OccCX if given separately, markedly increased DA when combined. These results indicate that endogenous 5-HT, raised by selective blockade of the 5-HT carrier, can increase extracellular DA in the OccCX and in the ParCX by stimulating 5-HT(1A) receptors independently from the presence of NA terminals, although blockade of 5-HT and NA carrier can strongly interact to raise extracellular DA in this area. These observations are consistent with the existence of DA neurons separate from the NA ones contributing to extracellular DA even in NA-rich/DA poor isocortical areas.


Subject(s)
Dopamine/metabolism , Extracellular Fluid/metabolism , Norepinephrine/metabolism , Prefrontal Cortex/drug effects , Receptor, Serotonin, 5-HT1A/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , Extracellular Fluid/drug effects , Male , Occipital Lobe/drug effects , Occipital Lobe/metabolism , Prefrontal Cortex/metabolism , Rats
8.
J Neurochem ; 88(4): 917-27, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14756813

ABSTRACT

This study compared the interaction between noradrenaline (NA) and dopamine (DA) mechanisms in the prefrontal (PFCX) and in the parietal (ParCX) and occipital (OccCX) cortex. The effect of reboxetine and desipramine, two NA transporter blockers, of mianserin, an antagonist of alpha2 and 5-HT2 receptors, and of clozapine, an atypical antipsychotic, on dialysate DA in the medial PFCX, ParCX and OccCX was studied. We also assessed the influence of a prior 6-hydroxydopamine (6-OHDA) lesion of the dorsal noradrenergic bundle (DNAB) on the effect of reboxetine and clozapine on dialysate DA in the PFCX and ParCX. Systemic administration of reboxetine and desipramine dose-dependently increased dialysate DA in the PFCX but not in the ParCX and OccCX. In contrast, mianserin and clozapine raised dialysate DA in the ParCX and OccCX to an even larger extent than in the PFCX. 6-OHDA lesions of DNAB abolished the increase of dialysate DA elicited by reboxetine in the PFCX and by clozapine both in the PFCX and in the ParCX. It is concluded that, although PFCX and ParCX/OccCX share the presence of a strong control of DA transmission by NA through alpha2 receptors, they differ in the extent to which DA is cleared from the extracellular compartment by uptake through the NA transporter. This process, although extensive in the PFCX, appears insignificant in the ParCX and OccCX, probably as a result of the higher ratio of NA to DA resulting in exclusion of DA from NA transporter.


Subject(s)
Cerebral Cortex/drug effects , Clozapine/pharmacology , Dopamine/metabolism , Mianserin/pharmacology , Serotonin Antagonists/pharmacology , Symporters/antagonists & inhibitors , Analysis of Variance , Animals , Cerebral Cortex/anatomy & histology , Cerebral Cortex/metabolism , Desipramine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Dose-Response Relationship, Drug , Drug Administration Routes , Drug Interactions , Extracellular Space/drug effects , Male , Microdialysis , Morpholines/pharmacology , Neural Pathways/injuries , Norepinephrine Plasma Membrane Transport Proteins , Oxidopamine/toxicity , Piperazines/pharmacology , Rats , Rats, Sprague-Dawley , Reboxetine , Time Factors
9.
Minerva Chir ; 52(5): 639-42, 1997 May.
Article in Italian | MEDLINE | ID: mdl-9297154

ABSTRACT

The authors report a case of Mirizzi's syndrome that was the cause of intrahepatic lithiasis. The recurrence of acute episodes of cholecystitis may lead to a partial obstruction of hepato-choledochal duct through compression and phlogosis (Type 1 Mirizzi's syndrome); moreover, the compression of calculous material wedged in the cystic duct may also result in ischemic necrosis of the wall, thus causing a cholecystic-choledochal internal biliary fistula (Type 2 Mirizzi's syndrome). The authors analyse problems relating to the complications of gallbladder calculosis with indications for surgery at the first symptomatic manifestation, given that the recurrence of cholecystic inflammatory episodes provokes pathological conditions in the biliary tract that require major surgery with a consequent increase in mortality and morbidity, above all in elderly patients. The authors recommended performing a through intraoperative study to ensure the correct identification of intrahepatic lithiasis, given the difficulty of preoperative diagnosis. The objective of treatment is to suppress the lithogenic focus and ensure good biliary drainage.


Subject(s)
Bile Ducts, Intrahepatic , Cholelithiasis/etiology , Cholestasis, Extrahepatic/etiology , Hepatic Duct, Common , Acute Disease , Aged , Bile Duct Diseases/diagnosis , Bile Duct Diseases/etiology , Bile Duct Diseases/surgery , Bile Ducts, Intrahepatic/surgery , Cholecystitis/complications , Cholelithiasis/complications , Cholelithiasis/diagnosis , Cholelithiasis/surgery , Cholestasis, Extrahepatic/diagnosis , Cholestasis, Extrahepatic/surgery , Female , Hepatic Duct, Common/surgery , Humans , Syndrome
10.
Minerva Anestesiol ; 63(4): 115-8, 1997 Apr.
Article in Italian | MEDLINE | ID: mdl-9380284

ABSTRACT

OBJECT: Evaluation of accuracy of three common dilution methods for drugs. EXPERIMENTAL PLAN: Perspective double blind investigation from March to June 1995. PLACE: Anaesthesia and Resuscitation Service of Children's Hospital of Iglesias (CA). METHODS: Forty dopamine at 2/1000 samples, obtained by dilution of dopamine at 40/1000 on sale with three different methods by five different operators, were analysed with a chromatography system in liquid phase at high pressure. RESULTS: Mean concentration with difference not exceeding 5% from the goal, are considered acceptable. Only one group of samples was found to be into these limits, but it was also the most dangerous for the high percentage of great mistakes in dilution. Although there are significant differences in the accuracy and safety of the three dilution methods, the highest and lowest final concentrations obtained differ very much from those estimated. CONCLUSIONS: It is suggested that drugs confections with proper dilution for different clinical uses might be on sale.


Subject(s)
Indicator Dilution Techniques , Reproducibility of Results
11.
Eur J Neurosci ; 9(10): 2077-85, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9421168

ABSTRACT

This study was performed to investigate the relative role of noradrenaline (NA) and dopamine (DA) carrier blockade in the effects of psychostimulants on DA transmission in the rat prefrontal cortex (PFCX). To this end, changes of extracellular DA and NA in the PFCX and of extracellular DA in the nucleus accumbens (NAc) were measured following the administration of amphetamine and cocaine, which are known to bind to both DA and NA carriers, or GBR 12909, a selective DA carrier blocker. After non-intravenous injection, amphetamine (0.25 and 0.5 mg/kg, s.c.) and cocaine (5 and 10 mg/kg, i.p.) increased extracellular DA in the PFCX to a larger extent than in the NAc, while the reverse applied to GBR 12909 (2.5 and 5 mg/kg, i.p.). These differences were obtained in spite of the fact that the three drugs elicited at each dose level a similar peak increase of extracellular DA in the NAc. Amphetamine and cocaine also increased extracellular NA in the PFCX and this effect was quantitatively similar to that on extracellular DA in the same area. Intravenous doses of cocaine and GBR 12909, corresponding to those which maintain self-administration in the rat, while equieffective in raising extracellular DA in the NAc, had different effects on extracellular DA in the PFCX. In fact, in contrast to cocaine, GBR 12909 increased extracellular DA in the PFCX to a lesser extent than in the NAc or did not modify it at all. The peak increase of extracellular DA in the PFCX was highly correlated to that of NA in the same area but was poorly correlated to the increase of extracellular DA in the NAc. These results suggest that amphetamine and cocaine increase extracellular DA in the PFCX largely through the blockade of the NA carrier. Direct evidence for this hypothesis was provided by the observation that, when the NA carrier was blocked by reverse dialysis of the PFCX with desipramine (1 microM), cocaine and GBR 12909 lost their differences in the ability to increase extracellular DA in the PFCX.


Subject(s)
Carrier Proteins/antagonists & inhibitors , Cocaine/pharmacology , Dextroamphetamine/pharmacology , Dopamine/pharmacology , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins , Norepinephrine/metabolism , Prefrontal Cortex/metabolism , Symporters , Animals , Desipramine/pharmacology , Dopamine Plasma Membrane Transport Proteins , Dopamine Uptake Inhibitors/pharmacology , Kinetics , Male , Multivariate Analysis , Norepinephrine Plasma Membrane Transport Proteins , Piperazines/pharmacology , Prefrontal Cortex/drug effects , Rats , Rats, Sprague-Dawley
12.
Psychopharmacology (Berl) ; 127(2): 83-7, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8888371

ABSTRACT

The effect of chronic administration of desipramine or fluoxetine (10 mg/kg IP once a day for 2 weeks) on extracellular noradrenaline; serotonin and dopamine in the rat prefrontal cortex was studied by transcerebral microdialysis. Chronic desipramine increased extracellular noradrenaline and dopamine by three-fold as compared to saline controls. Acute challenge with 10 mg/kg desipramine increased by more than three-fold extracellular noradrenaline and dopamine in saline controls, but failed further to increase extracellular noradrenaline and dopamine in rats chronically administered desipramine. Chronic fluoxetine more than doubled the extracellular concentrations of serotonin but failed to change the extracellular concentrations of dopamine as compared to saline controls. Challenge with 5 mg/kg fluoxetine while almost doubling extracellular serotonin and dopamine concentrations in saline controls, failed further to increase extracellular serotonin and did not change extracellular dopamine in rats chronically exposed to fluoxetine. In contrast, challenge with 10 mg/kg desipramine normally increased extracellular dopamine in rats chronically exposed to fluoxetine. Therefore, chronic fluoxetine is associated with normal presynaptic dopamine transmission in the prefrontal cortex as a result of tolerance to fluoxetine-induced increase of extracellular dopamine; in contrast, chronic desipramine is associated with an increase of pre-synaptic dopamine transmission in the prefrontal cortex up to a level that cannot be further elevated by acute desipramine challenge. The results suggest that prefrontal cortex dopamine plays a different role in the antidepressant properties of desipramine and fluoxetine.


Subject(s)
Desipramine/pharmacology , Dopamine/analysis , Fluoxetine/pharmacology , Prefrontal Cortex/drug effects , Animals , Male , Norepinephrine/analysis , Prefrontal Cortex/chemistry , Rats , Rats, Sprague-Dawley
13.
Psychopharmacology (Berl) ; 119(1): 15-9, 1995 May.
Article in English | MEDLINE | ID: mdl-7675944

ABSTRACT

Fluoxetine and desipramine, two antidepressants that block selectively the serotonin and the noradrenaline carrier, increase extracellular dopamine concentrations in the prefrontal cortex of freely-moving rats. This effect is calcium dependent and is prevented, in the case of fluoxetine but not desipramine, by systemic pretreatment with low doses or by low concentrations in the dialyzing Ringer of the potent 5-HT3 antagonist ICS 205930. Fluoxetine, but not desipramine, increases extracellular serotonin concentrations in the prefrontal cortex. The results indicate that selective serotonin reuptake blockers increase extracellular dopamine in the prefrontal cortex by stimulating local 5-HT3 receptors.


Subject(s)
Desipramine/pharmacology , Fluoxetine/pharmacology , Receptors, Serotonin/drug effects , Animals , Dopamine/metabolism , Frontal Lobe/metabolism , Male , Microdialysis , Rats , Rats, Sprague-Dawley , Serotonin/metabolism , Time Factors
14.
Psychopharmacology (Berl) ; 115(1-2): 285-8, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7862908

ABSTRACT

Drugs differing in their primary mechanism of action but having in common the ability to act as antidepressants such as fluoxetine (10 mg/kg SC), clomipramine (10 mg/kg IP), imipramine (10 mg/kg IP), desipramine (10 mg/kg IP) and (+/-) 8-OHDPAT (0.03 mg/kg SC) increase extracellular concentrations of dopamine in the rat prefrontal cortex but not in the medial nucleus accumbens. Buspirone (1 mg/kg SC) increased dopamine both in the prefrontal cortex and in the nucleus accumbens. Extracellular 5HT was increased by fluoxetine, clomipramine and imipramine but not by desipramine while 8-OHDPAT and buspirone decreased it. These results raise the possibility that the property of stimulating dopamine transmission in the prefrontal cortex has a role in the antidepressant properties of these drugs.


Subject(s)
Antidepressive Agents/pharmacology , Dopamine/metabolism , Extracellular Space/metabolism , Prefrontal Cortex/metabolism , Animals , Antidepressive Agents, Second-Generation/pharmacology , Antidepressive Agents, Tricyclic/pharmacology , Extracellular Space/drug effects , Histocytochemistry , Male , Microdialysis , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Prefrontal Cortex/anatomy & histology , Prefrontal Cortex/drug effects , Rats , Rats, Sprague-Dawley , Serotonin/metabolism
15.
Psychopharmacology (Berl) ; 112(2-3): 398-402, 1993.
Article in English | MEDLINE | ID: mdl-7871048

ABSTRACT

Concentric dialysis probes were vertically implanted in rats in the nucleus accumbens (Acc) of one side and in the dorsal caudate-putamen (CPu) of the other side. On the day after the implant the output of dopamine was monitored and the changes elicited by d-amphetamine sulphate were compared in the two areas. Amphetamine preferentially stimulated dopamine release in the Acc in a wide range of doses (0.25, 0.5, 1.0, 2.0 mg/kg SC) when Acc probes were located in the medial aspect of the Acc. In contrast, no significant differences between the Acc and the dorsal CPu were obtained in response to amphetamine (0.5 mg/kg SC) when Acc probes were located about 0.7 mm lateral to the previous site. It is concluded that the preferential effect of amphetamine in the Acc is related to precise topographical boundaries. This in turn might be related to the existence of a sharp anatomical and functional heterogeneity within the Acc.


Subject(s)
Amphetamine/pharmacology , Dopamine/metabolism , Nucleus Accumbens/metabolism , Animals , Caudate Nucleus/anatomy & histology , Caudate Nucleus/drug effects , Caudate Nucleus/metabolism , Chromatography, High Pressure Liquid , Male , Microdialysis , Nucleus Accumbens/anatomy & histology , Nucleus Accumbens/drug effects , Putamen/anatomy & histology , Putamen/drug effects , Putamen/metabolism , Rats , Rats, Sprague-Dawley
16.
Neurochem Int ; 20 Suppl: 231S-235S, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1365432

ABSTRACT

The effect of systemic administration of desmethylimipramine (DMI), an inhibitor of the noradrenaline (NA) reuptake carrier, and of GBR 12909, an inhibitor of the dopamine (DA) reuptake carrier, on the in vivo extracellular concentrations of dopamine (DA) was studied by transcerebral dialysis in the prefrontal cortex and in the dorsal caudate of freely moving rats. In the NA-rich prefrontal cortex only DMI increased extracellular DA concentrations whereas in the dorsal caudate only GBR 12909 was effective. Haloperidol increased extracellular DA concentrations more effectively in the dorsal caudate than in the prefrontal cortex. Pretreatment with DMI, which failed to modify the effect of haloperidol in the dorsal caudate, potentiated its action in the prefrontal cortex. The reverse was obtained after GBR 12909+ haloperidol in the two areas. 6-hydroxydopamine lesioning of the dorsal NA bundle prevented the ability of DMI to increase DA concentrations. The results suggest that reuptake into NA terminals is an important mechanism by which DA is cleared from the extracellular space in a NA-rich area such as the prefrontal cortex. The elevated extracellular concentrations of DA resulting from blockade of such mechanism by tricyclic antidepressants may play a role in the therapeutic effects of these drugs.


Subject(s)
Biogenic Monoamines/metabolism , Carrier Proteins/metabolism , Desipramine/pharmacology , Neurons/metabolism , Neurotransmitter Agents/metabolism , Piperazines/pharmacology , Animals , Carrier Proteins/antagonists & inhibitors , Caudate Nucleus/metabolism , Dopamine/metabolism , Haloperidol/pharmacology , Male , Neurotransmitter Uptake Inhibitors/pharmacology , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley
17.
Tissue Antigens ; 39(2): 78-83, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1349446

ABSTRACT

This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.


Subject(s)
Celiac Disease/genetics , Gene Frequency/genetics , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , HLA-DR3 Antigen/genetics , Haplotypes/genetics , Adult , Celiac Disease/epidemiology , Celiac Disease/immunology , Child , Disease Susceptibility , Gene Amplification/genetics , Gene Frequency/immunology , HLA-A Antigens/immunology , HLA-B Antigens/immunology , HLA-B18 Antigen , HLA-DQ Antigens/immunology , HLA-DQ alpha-Chains , HLA-DR Antigens/immunology , HLA-DR Serological Subtypes , HLA-DR3 Antigen/immunology , Haplotypes/immunology , Humans , Italy/epidemiology , Linkage Disequilibrium , Middle Aged , Polymorphism, Restriction Fragment Length
18.
J Neurochem ; 55(3): 1067-70, 1990 Sep.
Article in English | MEDLINE | ID: mdl-2117046

ABSTRACT

The effect of systemic administration of desmethylimipramine (DMI) and oxaproptiline (OXA), two inhibitors of the noradrenaline (NA) reuptake carrier, on the in vivo extracellular concentrations of dopamine (DA) was studied by transcerebral dialysis in the prefrontal cortex and in the dorsal caudate of freely moving rats. In the NA-rich prefrontal cortex, either drug increased extracellular DA concentrations whereas in the dorsal caudate neither was effective. Haloperidol increased extracellular DA concentrations more effectively in the dorsal caudate than in the prefrontal cortex. Pre-treatment with DMI or OXA, which failed to modify the effect of haloperidol in the dorsal caudate, potentiated its action in the prefrontal cortex. 6-Hydroxydopamine lesioning of the dorsal NA bundle prevented the ability of OXA to increase DA concentrations. The results suggest that reuptake into NA terminals in an important mechanism by which DA is cleared from the extracellular space in a NA-rich area such as the prefrontal cortex. The elevated extracellular concentrations of DA resulting from blockade of such mechanism by tricyclic antidepressants may play a role in the therapeutic effects of these drugs.


Subject(s)
Dopamine/metabolism , Frontal Lobe/metabolism , Norepinephrine/antagonists & inhibitors , Animals , Caudate Nucleus/drug effects , Caudate Nucleus/metabolism , Desipramine/pharmacology , Drug Synergism , Extracellular Space/metabolism , Frontal Lobe/drug effects , Haloperidol/pharmacology , Hydroxydopamines/pharmacology , Male , Maprotiline/analogs & derivatives , Maprotiline/pharmacology , Oxidopamine , Rats , Rats, Inbred Strains
19.
Eur J Pharmacol ; 164(3): 515-9, 1989 May 30.
Article in English | MEDLINE | ID: mdl-2767122

ABSTRACT

The effects of a potent and specific antagonist of 5-HT3 receptors, ICS 205-930, on the dopamine (DA)-releasing properties of morphine (1.0 mg/kg s.c.), nicotine (0.6 mg/kg s.c.), ethanol (1.0 g/kg i.p.) and amphetamine (0.25 and 1.0 mg/kg s.c.) were studied in rats. DA release was estimated by trans-cerebral dialysis in the nucleus accumbens of freely moving rats. ICS 205-930 (15-30 micrograms/kg s.c.) failed to modify the basal output of DA and its metabolites, however, ICS 205-930 dose dependently reduced the stimulation of DA release by morphine, nicotine and ethanol. Thus, at doses of 30 micrograms/kg s.c., ICS 205-930 completely prevented the morphine-, nicotine- and ethanol-induced stimulation of DA release in the nucleus accumbens; doses of 15 micrograms/kg s.c. partially prevented the morphine-, nicotine- and ethanol-induced stimulation of DA release while doses of 7.5 micrograms/kg s.c. were ineffective. In contrast, ICS 205-930 (up to 30 micrograms/kg s.c.) failed to affect the amphetamine-induced stimulation of DA release in the nucleus accumbens. The inhibitory effects of ICS 205-930 (15 and 30 micrograms/kg s.c.) on the drug-induced stimulation of DA release could also be extended to the neuroleptic haloperidol (0.1 mg/kg s.c.). The results indicate that blockade of 5-HT3 receptors selectively prevents the stimulation of DA release induced by drugs known to stimulate the firing activity of DA neurons.


Subject(s)
Dopamine/metabolism , Serotonin Antagonists/pharmacology , Amphetamine/pharmacology , Animals , Brain Chemistry/drug effects , Dialysis , Ethanol/pharmacology , Haloperidol/pharmacology , Indoles/pharmacology , Male , Morphine/pharmacology , Nicotine/pharmacology , Rats , Rats, Inbred Strains , Tropisetron
20.
J Pharmacol Exp Ther ; 245(1): 257-64, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3258912

ABSTRACT

Using the technique of brain dialysis in freely moving rats we have investigated the effect of various dopamine (DA) receptor agonists on the release and metabolism of DA in two terminal dopaminergic areas, the nucleus accumbens and the dorsal caudate. Low doses of various DA receptor agonists such as apomorphine (12-100 micrograms/kg s.c.), LY 171555 (5-50 micrograms/kg s.c.), pergolide (5-25 micrograms/kg s.c.), (+)-3PPP (0.5-2.5 mg/kg s.c.) and BHT 920 (10-250 micrograms/kg s.c.) reduce DA release and elicit hypomotility. The potency of the drugs and their effectiveness is similar in the two areas. Inhibition of DA release appears related to the ability of the various agonists to stimulate D-2 rather than D-1 receptors. Thus, the reportedly selective D-1 agonist, SKF 38393, was inactive on DA release and metabolism even at doses fully active in eliciting D-1-mediated effects (grooming); on the other hand apomorphine, a D-1/D-2 agonist, and pergolide, a D-2 agonist with rather weak D-1 activity, reduced DA release in a manner which was related to their agonist activity at D-2 receptors; finally LY 171555, (+)-3PPP and BHT 920, which selectively stimulate D-2 receptors, were fully active at reducing DA release in vivo. Apomorphine, pergolide, LY 171555 and (+)-3PPP given at higher doses elicited behavioral stimulation. In contrast, BHT 920 failed to do so. In further contrast (-)-3PPP (0.1-10 mg/kg s.c.), which failed to reduce DA release at low doses, actually stimulated it at high doses (10 mg/kg s.c.) and elicited hypomotility, thus resembling DA receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Behavior, Animal/drug effects , Brain/metabolism , Receptors, Dopamine/metabolism , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Apomorphine/pharmacology , Azepines/pharmacology , Benzazepines/pharmacology , Dialysis , Dopamine/metabolism , Ergolines/pharmacology , Homovanillic Acid/metabolism , Isomerism , Male , Motor Activity/drug effects , Neurons/metabolism , Pergolide/pharmacology , Piperidines/pharmacology , Quinpirole , Rats , Rats, Inbred Strains , Time Factors
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