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1.
Behav Brain Res ; 449: 114462, 2023 07 09.
Article in English | MEDLINE | ID: mdl-37121276

ABSTRACT

Previously we showed that Deep Brain Stimulation (DBS) of the dorsal region (DRD) and of the lateral wings of the dorsal raphe (lwDR) respectively decreases anxiety and panic-like responses in the elevated T-maze (ETM). This study investigates neurobiological alterations which might respond for these behavioral effects. Male Wistar rats were submitted to high-frequency stimulation (100 µA, 100 Hz) of the DRD or of the lwDR for 1 h, and subsequently tested in the avoidance or escape tasks of the ETM. Since serotonin (5-HT) reuptake inhibitors are first line pharmacological treatment for anxiety disorders, we also tested the effects of chronic fluoxetine administration (10 mg/kg, IP, 21 days) on a separate group of rats. An open field was used for locomotor activity assessment. Additionally, we evaluated c-Fos immunoreactivity (Fos-ir) in serotonergic cells of the dorsal raphe (DR). Results showed that DBS of the DRD decreases avoidance reactions, an anxiolytic-like effect, without altering escape or locomotor activity. Both fluoxetine and DBS of the lwDR decreased escape responses in the ETM, a panicolytic-like effect, without altering avoidance measurements or locomotor activity. While DBS of the DRD decreased double immunostaining in the DRD, DBS of the lwDR increased Fos-ir and double immunostaining in the DRD and lwDR. Fluoxetine also increased double immunostaining in the lwDR and in the DRV but decreased it in the DRD. These results suggest that both the anxiolytic and panicolytic-like effects of DBS and fluoxetine are related to 5-HT modulation in different subnuclei of the DR.


Subject(s)
Anti-Anxiety Agents , Deep Brain Stimulation , Rats , Male , Animals , Anti-Anxiety Agents/pharmacology , Dorsal Raphe Nucleus , Serotonin/pharmacology , Fluoxetine/pharmacology , Rats, Wistar , Escape Reaction/physiology , Anxiety/drug therapy
2.
Behav Brain Res ; 403: 113134, 2021 04 09.
Article in English | MEDLINE | ID: mdl-33476685

ABSTRACT

In a previous study we showed that Deep Brain Stimulation (DBS) of the rat dorsal subregion of the dorsal raphe (DRD), which sends serotonergic projections to forebrain areas, such as the ventral hippocampus, induces anxiolytic-like effects. The purpose of the present study was to investigate neurobiological alterations which might underline these behavioral effects. For that, we tested the influence of DBS upon the neuromodulatory action of serotonin on excitatory post-synaptic currents (EPSCs) in the ventral hippocampus. Male Wistar rats were submitted to high-frequency stimulation (100 µA, 100 Hz) of the DRD for 1 h during three consecutive days. On the third day, immediately after the DBS procedure, animals were euthanized. Slices of the ventral hippocampus were processed for whole cell patch clamp recordings of AMPA-receptor (AMPAR) mediated EPSCs in the CA1 area. As reported by others, we confirmed that in pre-weaning rats a high affinity 5-HT1A receptor agonist (8-OH-PIPAT, 0.5-5nM) inhibits EPSCs. However, in adult rats (non-operated or sham-operated), 8-OH-PIPAT (0.5-5 nM) increased EPSC amplitude, an effect blocked by the 5-HT1A antagonist WAY-100,635 (200 nM). Importantly, in adult rats exposed to DBS, the 5-HT1A agonist was devoid of effect. Taken together these results show that: 1) changes in 5-HT1A receptor-mediated hippocampal synaptic transmission occur with age; 2) these changes lead to a facilitatory effect of 5-HT1A receptors; 3) DBS blocks this serotonergic facilitatory action. These observations suggest that an alteration in serotonin modulation of limbic areas may underlie the psychotherapeutic effects of DBS.


Subject(s)
CA1 Region, Hippocampal/physiology , Deep Brain Stimulation , Dorsal Raphe Nucleus , Excitatory Postsynaptic Potentials/physiology , Receptor, Serotonin, 5-HT1A/metabolism , Receptors, AMPA/metabolism , Serotonin 5-HT1 Receptor Agonists/pharmacology , Synaptic Transmission/physiology , Age Factors , Animals , CA1 Region, Hippocampal/drug effects , CA1 Region, Hippocampal/metabolism , Excitatory Postsynaptic Potentials/drug effects , Male , Rats , Rats, Wistar , Receptor, Serotonin, 5-HT1A/drug effects , Synaptic Transmission/drug effects
3.
Anaerobe ; 59: 145-153, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31254652

ABSTRACT

Glycerol, the main residue of biodiesel production, can be used to produce organic acids and energy through anaerobic digestion. This study aimed to assess microbial structure, diversity, productivity, and stability and the influence of these parameters on the performance of an anaerobic reactor. The experimental setup consisted of an upflow anaerobic sludge blanket (UASB) reactor fed residual glycerol and nutrients. The organic loading rate (OLR) was gradually increased through five stages, and sludge samples were collected at each, followed by DNA extraction and PCR denaturing gradient gel electrophoresis (PCR-DGGE). The resulting bands were excised, amplified, and purified. The results showed increased bacterial diversity and richness from the inoculum (Rr 38.72 and H 2.32) and along stages I and II, reaching the highest populational parameters (Rr 194.06 and H 3.32). The following stages promote decreases in richness and diversity, achieving the lowest populational parameters on this study (Rr 11.53 and H 2.04). Biogas production increased along with functional organization due to the specialization of the bacterial community and a decrease in the methanogenic population, both promoted by the increase in OLR.


Subject(s)
Archaea/classification , Archaea/isolation & purification , Bacteria, Anaerobic/classification , Bacteria, Anaerobic/isolation & purification , Bioreactors/microbiology , Biota , Glycerol/metabolism , Anaerobiosis , Carboxylic Acids/metabolism
4.
Biotechnol Lett ; 36(7): 1381-90, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24737072

ABSTRACT

The fermentative production of H2 from residual glycerol is an attractive alternative for clean energy production from a waste product. Selection of operational variables for microbial populations with an adequate diversity in order to improve H2 yields is an issue faced during optimization of biological production of H2. Operational and environmental factors affect both microbial diversity and the activity of specific enzymes. Therefore, these variables must be controlled to obtain the best H2 yields. This review covers the main variables involved in the fermentative production of H2 from crude glycerol and the biochemistry of the anaerobic digestion of glycerol, with a focus on the microbial diversity involved in this process.


Subject(s)
Bacteria/growth & development , Bacteria/metabolism , Biotechnology/methods , Gases/metabolism , Glycerol/metabolism , Hydrogen/metabolism , Biodiversity , Fermentation
5.
Behav Brain Res ; 268: 8-13, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-24667361

ABSTRACT

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. In addition, it has also been implicated in the processing of acoustic information of aversive nature, as well as in sensory-motor gating. There is evidence that glutamate-mediated mechanisms at the IC level influence haloperidol-induced catalepsy. The present study investigated the influence of glutamate-mediated mechanisms in the IC on catalepsy induced by intrastriatal microinjection of haloperidol (10 µg/0.5 µl). Male Wistar rats received bilateral intracollicular microinjections of the glutamate receptor agonist NMDA (10 or 20 nmol/0.5 µl), the NMDA receptor antagonists MK-801 (15 or 30 nmol/0.5 µl) or physiological saline (0.5 µl), followed by bilateral microinjections of haloperidol (10 µg/0.5 µl) or vehicle (0.5 µl) into the dorso-rostral or ventro-rostral striatum. The catalepsy test was performed positioning both forepaws of the rats on an elevated horizontal wooden bar and recording the time during which the animal remained in this position. The results showed that the administration of physiological saline in the IC followed by the microinjection of haloperidol in the dorso-rostral region of the striatum was not able to induce catalepsy. However, when the bilateral administration of NMDA into the IC was followed by microinjection of haloperidol into the dorso-rostral striatum, catalepsy was observed. The microinjection of haloperidol into the ventro-rostral striatum induced catalepsy, counteracted by previous administration of MK-801 into the IC. These findings suggest that glutamate-mediated mechanisms in the IC can influence the intrastriatal haloperidol-induced catalepsy and that the IC plays an important role as a sensorimotor interface.


Subject(s)
Antipsychotic Agents/adverse effects , Catalepsy/chemically induced , Glutamic Acid/metabolism , Haloperidol/adverse effects , Inferior Colliculi/drug effects , Inferior Colliculi/physiopathology , Animals , Catalepsy/physiopathology , Corpus Striatum/drug effects , Corpus Striatum/physiopathology , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Male , N-Methylaspartate/metabolism , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/agonists , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Synaptic Transmission/drug effects , Synaptic Transmission/physiology
6.
Behav Brain Res ; 250: 81-90, 2013 Aug 01.
Article in English | MEDLINE | ID: mdl-23644183

ABSTRACT

Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis.


Subject(s)
Anxiety/etiology , Anxiety/pathology , Hippocampus/metabolism , Neurogenesis/physiology , Oncogene Proteins v-fos/metabolism , Analysis of Variance , Animals , Avoidance Learning , Corticosterone/blood , Disease Models, Animal , Doublecortin Domain Proteins , Doublecortin Protein , Escape Reaction , Male , Maze Learning , Mice , Microtubule-Associated Proteins/metabolism , Neuropeptides/metabolism , Rats, Wistar , Reaction Time/physiology , Stress, Psychological/complications , Time Factors
8.
Behav Brain Res ; 238: 170-7, 2013 Feb 01.
Article in English | MEDLINE | ID: mdl-23098799

ABSTRACT

In a previous study we showed that rats chronically treated with corticosterone (CORT) display anxiogenic behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. Treatment with the tricyclic antidepressant imipramine significantly reversed the anxiogenic effects of CORT, while inhibiting ETM escape, a response related to panic disorder. To better understand the neurobiological mechanisms underlying these behavioral effects, analysis of c-fos protein immunoreactivity (fos-ir) was used here to map areas activated by chronic CORT (200 mg pellets, 21-day release) and imipramine (15 mg/kg, IP) administration. We also evaluated the number of cells expressing the neurogenesis marker doublecortin (DCX) in the hippocampus and measured plasma CORT levels on the 21st day of treatment. Results showed that CORT increased fos-ir in the ventrolateral septum, medial amygdala and paraventricular hypothalamic nucleus and decreased fos-ir in the lateral periaqueductal gray. Imipramine, on the other hand, increased fos-ir in the medial amygdala and decreased fos-ir in the anterior hypothalamus. CORT also decreased the number of DCX-positive cells in the ventral and dorsal hippocampus, an effect antagonized by imipramine. CORT levels were significantly higher after treatment. These data suggest that the behavioral effects of CORT and imipramine are mediated through specific, at times overlapping, neuronal circuits, which might be of relevance to a better understanding of the physiopathology of generalized anxiety and panic disorder.


Subject(s)
Corticosterone/administration & dosage , Hippocampus/drug effects , Imipramine/administration & dosage , Neurogenesis/drug effects , Proto-Oncogene Proteins c-fos/metabolism , Amygdala/drug effects , Amygdala/metabolism , Animals , Doublecortin Domain Proteins , Doublecortin Protein , Hippocampus/metabolism , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Microtubule-Associated Proteins/metabolism , Neurogenesis/physiology , Neurons/drug effects , Neurons/metabolism , Neuropeptides/metabolism , Rats , Rats, Wistar
9.
Water Sci Technol ; 66(10): 2217-22, 2012.
Article in English | MEDLINE | ID: mdl-22949254

ABSTRACT

Crude glycerol, the main by-product of the biodiesel industry, is a material containing compounds considered recalcitrant to microorganisms. The aims of this study were to determine the anaerobic biodegradability and the methane production potential (MPP) of different crude glycerols generated from the transesterification of oils from several kinds of seeds and/or beans, and the anaerobic toxicity of crude glycerol obtained from a mixture of soybean and cottonseed oils. All tests were based on specific methanogenic activity assays (SMA). The biodegradability tests and the MPP assays lasted 30 days. Toxicity was evaluated through the statistical technique of factorial design and a response surface was generated in which the concentrations of crude glycerol and glucose were the independent variables and SMA was the dependent variable. The results showed that the type of seed or bean, as well as the transesterification process, affected the anaerobic biodegradability. Biodegradability ranged between 65.9 and 85.6% and MPP, between 0.220 and 0.322 m(3) CH(4)/kg crude glycerol. The toxicity test showed that crude glycerol was not toxic to anaerobic sludge.


Subject(s)
Biodegradation, Environmental , Biofuels/analysis , Glycerol/metabolism , Methane/metabolism , Anaerobiosis , Glycerol/chemistry , Industrial Waste , Methane/chemistry , Waste Disposal, Fluid/methods , Water Pollutants, Chemical
10.
Behav Brain Res ; 232(1): 20-9, 2012 Jun 15.
Article in English | MEDLINE | ID: mdl-22487246

ABSTRACT

Results from a previous study show that rats exposed to acute restraint display anxiogenic-like behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. In contrast, escape responses were unaltered by stress exposure. Since ETM avoidance and escape tasks seem to activate distinct sets of brain structures, it is possible that the differences observed with acute restraint are due to particularities in the neurobiological mechanisms which modulate these responses. In the present study, analysis of fos protein immunoreactivity (fos-ir) was used to map areas activated by exposure of male Wistar rats to restraint stress (30 min) previously (30 min) to the ETM. Corticosterone levels were also measured in stressed and non-stressed animals. Confirming previous observations restraint facilitated avoidance performance, an anxiogenic result, while leaving escape unaltered. Performance of the avoidance task increased fos-ir in the frontal cortex, intermediate lateral septum, basolateral amygdala, basomedial amygdala, lateral amygdala, anterior hypothalamus and dorsal raphe nucleus. In contrast, performance of escape increased fos-ir in the ventromedial hypothalamus, dorsolateral periaqueductal gray and locus ceruleus. Both behavioral tasks also increased fos-ir in the dorsomedial hypothalamus. Restraint significantly raised corticosterone levels. Additionally after restraint, fos-ir was predominantly seen in the basolateral amygdala and dorsal raphe of animals submitted to the avoidance task. This data confirms that different sets of brain structures are activated by ETM avoidance and escape tasks and suggests that acute restraint differently alters ETM behavior and the pattern of fos activation in the brain.


Subject(s)
Brain Chemistry/physiology , Escape Reaction/physiology , Oncogene Proteins v-fos/biosynthesis , Stress, Psychological/metabolism , Stress, Psychological/psychology , Animals , Anxiety/psychology , Avoidance Learning/physiology , Corticosterone/blood , Data Interpretation, Statistical , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Immunohistochemistry , Male , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/metabolism , Rats , Rats, Wistar , Restraint, Physical
11.
Braz. j. med. biol. res ; 45(3): 238-243, Mar. 2012. ilus, tab
Article in English | LILACS | ID: lil-618055

ABSTRACT

Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant’s anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.


Subject(s)
Animals , Male , Rats , Anti-Anxiety Agents/administration & dosage , Anxiety/drug therapy , Avoidance Learning/drug effects , Behavior, Animal/drug effects , Lippia/chemistry , Monoterpenes/administration & dosage , Oils, Volatile/administration & dosage , Dose-Response Relationship, Drug , Rats, Wistar
12.
Braz J Med Biol Res ; 45(3): 238-43, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22358424

ABSTRACT

Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.


Subject(s)
Anti-Anxiety Agents/administration & dosage , Anxiety/drug therapy , Avoidance Learning/drug effects , Behavior, Animal/drug effects , Lippia/chemistry , Monoterpenes/administration & dosage , Oils, Volatile/administration & dosage , Animals , Cyclohexane Monoterpenes , Dose-Response Relationship, Drug , Male , Rats , Rats, Wistar
13.
Behav Brain Res ; 226(1): 50-5, 2012 Jan 01.
Article in English | MEDLINE | ID: mdl-21907244

ABSTRACT

Serotonin in the lateral septum has been implicated in the modulation of defense and hence in anxiety. However, it deserves investigation how changes in 5-HT-mechanisms in this area modulate defensive responses associated with specific subtypes of anxiety disorders. We evaluated the effects of intra-dorsolateral septum (DLS) injections of the preferential 5-HT(2A) receptor agonist DOI (8 and 16nmol), the 5-HT(2C) selective agonist MK-212 (0.1 and 1nmol) and the preferential 5-HT(2A) antagonist ketanserin (10 and 20nmol) in rats exposed to the elevated T-maze (ETM), a model which allows the measurement of two defensive responses: inhibitory avoidance and escape. These responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open-field after the ETM for locomotor activity assessments. Results showed that intra-DLS DOI increased avoidance latencies, an anxiogenic effect. MK and ketanserin were without effect. Also, none of the drugs administered affected the escape performance. Ketanserin blocked the anxiogenic effect caused by DOI. No changes to locomotion were observed. The data suggests that DLS 5-HT(2A) receptors are involved in the control of inhibitory avoidance and that a failure in this mechanism may be of importance to the physiopathology of generalized anxiety.


Subject(s)
Anxiety/metabolism , Escape Reaction/physiology , Receptor, Serotonin, 5-HT2A/metabolism , Septum of Brain/metabolism , Amphetamines/pharmacology , Animals , Anxiety/physiopathology , Avoidance Learning/drug effects , Avoidance Learning/physiology , Escape Reaction/drug effects , Ketanserin/pharmacology , Male , Rats , Rats, Wistar , Septum of Brain/drug effects , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology
14.
Braz. j. med. biol. res ; 44(10): 1048-1053, Oct. 2011. ilus
Article in English | LILACS | ID: lil-600686

ABSTRACT

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.


Subject(s)
Animals , Male , Rats , Antidepressive Agents, Tricyclic/administration & dosage , Anxiety/drug therapy , Behavior, Animal/drug effects , Corticosterone/administration & dosage , Imipramine/administration & dosage , Panic Disorder/drug therapy , Antidepressive Agents, Tricyclic/pharmacology , Corticosterone/pharmacology , Escape Reaction/drug effects , Imipramine/pharmacology , Maze Learning/drug effects , Motor Activity/drug effects , Rats, Wistar
15.
Braz J Med Biol Res ; 44(10): 1048-53, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21915474

ABSTRACT

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.


Subject(s)
Antidepressive Agents, Tricyclic/administration & dosage , Anxiety/drug therapy , Behavior, Animal/drug effects , Corticosterone/administration & dosage , Imipramine/administration & dosage , Panic Disorder/drug therapy , Animals , Antidepressive Agents, Tricyclic/pharmacology , Corticosterone/pharmacology , Escape Reaction/drug effects , Imipramine/pharmacology , Male , Maze Learning/drug effects , Motor Activity/drug effects , Rats , Rats, Wistar
16.
Int J Lab Hematol ; 33(6): 566-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21470372

ABSTRACT

INTRODUCTION: Several hemoglobin variants have electrophoretic behavior similar to hemoglobin S, which may lead to false diagnosis for sickle-cell disorders in newborn screening programs. A homozygous hemoglobin with S mobility was detected in two unrelated babies in Brazil. METHODS: Isoelectric focusing and high-performance liquid chromatography assays, gene sequencing, and restriction fragment length polymorphism with AfeI were used to characterize the hemoglobin. RESULTS: Hb Stanleyville-II and -α(3.7) /-α(3.7) type I deletion in the α-globin gene was diagnosed. Parents were heterozygous for both Hb Stanleyville-II and α-thalassemia. Hypochromia and microcytosis were probably due to the homozygous α-thalassemia. CONCLUSION: Stanleyville-II gene mutation is HBA2:c.237C>A, or C>G, and this information on the Globin Gene Server should be updated; AfeI test is a fast and accurate method to detect it; NBS programs should consider the possibility of Hb Stanleyville-II whenever IEF shows one band in the HbS position, and another one between S and C.


Subject(s)
Hemoglobins, Abnormal/genetics , Mutation, Missense , alpha-Globins/genetics , alpha-Thalassemia/genetics , Base Sequence , Brazil , DNA Mutational Analysis , Family Health , Genotype , Homozygote , Humans , Infant, Newborn , Molecular Sequence Data
17.
Behav Brain Res ; 216(2): 692-8, 2011 Jan 20.
Article in English | MEDLINE | ID: mdl-20883726

ABSTRACT

Previous evidence has shown that facilitation of GABA/benzodiazepine-mediated neurotransmission in the ventromedial hypothalamus (VMH) inhibits both escape and inhibitory avoidance responses generated in the elevated T-maze test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Aside from GABA/benzodiazepine receptors, the VMH also contains a significant number of serotonin (5-HT) receptors, including 1A, 2A and 2C subtypes. The purpose of the present study was to investigate the effect of the activation of 5-HT(1A) and 5-HT(2A/2C) receptors in the VMH on defensive behavioral responses in rats submitted to the ETM. For that, male Wistar rats were treated intra-VMH with the 5-HT(1A) agonist 8-OH-DPAT, with the 5-HT(2A/2C) agonist DOI, with the 5-HT(2C) selective agonist MK-212, or with the 5-HT(2A/2C) antagonist ketanserin and 10 min after were submitted to the ETM. Results showed that both DOI and MK-212 significantly decreased avoidance measurements, an anxiolytic-like effect, without altering escape. 8-OH-DPAT and ketanserin were without effect, although the last drug attenuated the effects of DOI. None of the drugs altered locomotor activity in an open field. These results suggest that 5-HT(2A/2C) receptors of the VMH are involved in the regulation of inhibitory avoidance and might be of relevance to the physiopathology of generalized anxiety.


Subject(s)
Anxiety/prevention & control , Receptor, Serotonin, 5-HT2A/physiology , Receptor, Serotonin, 5-HT2C/physiology , Serotonin Agents/pharmacology , Ventromedial Hypothalamic Nucleus/drug effects , Animals , Anxiety/physiopathology , Avoidance Learning/drug effects , Avoidance Learning/physiology , Escape Reaction/drug effects , Escape Reaction/physiology , Exploratory Behavior/drug effects , Exploratory Behavior/physiology , Male , Maze Learning/drug effects , Maze Learning/physiology , Motor Activity/drug effects , Motor Activity/physiology , Rats , Rats, Wistar , Receptor, Serotonin, 5-HT2A/drug effects , Receptor, Serotonin, 5-HT2C/drug effects , Ventromedial Hypothalamic Nucleus/physiology
18.
Braz. j. med. biol. res ; 43(9): 869-873, Sept. 2010. ilus
Article in English | LILACS | ID: lil-556857

ABSTRACT

The medial hypothalamus is part of a neurobiological substrate controlling defensive behavior. It has been shown that a hypothalamic nucleus, the dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a defensive behavior related to panic attacks. The role played by the DMH in the organization of conditioned fear responses, however, is less clear. In the present study, we investigated the effects of reversible inactivation of the DMH with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape expression by male Wistar rats (approximately 280 g in weight) tested in the elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive response, has been associated with generalized anxiety disorder. Results showed that intra-DMH administration of the GABA A receptor agonist muscimol inhibited escape performance, suggesting an antipanic-like effect (P < 0.05), without changing inhibitory avoidance acquisition. Although a higher dose of muscimol (1.0 nmol/0.2 µL; N = 7) also altered locomotor activity in an open field when compared to control animals (0.2 µL saline; N = 13) (P < 0.05), the lower dose (0.5 nmol/0.2 µL; N = 12) of muscimol did not cause any motor impairment. These data corroborate previous evidence suggesting that the DMH is specifically involved in the modulation of escape. Dysfunction of this regulatory mechanism may be relevant in the genesis/maintenance of panic disorder.


Subject(s)
Animals , Male , Rats , Anxiety Disorders/physiopathology , GABA-A Receptor Agonists/pharmacology , Hypothalamus/drug effects , Muscimol/pharmacology , Panic Disorder/etiology , Panic Disorder/physiopathology , Anxiety Disorders/etiology , Escape Reaction/drug effects , Hypothalamus/physiopathology , Maze Learning/drug effects , Motor Activity/drug effects , Rats, Wistar
19.
Braz J Med Biol Res ; 43(9): 869-73, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20694443

ABSTRACT

The medial hypothalamus is part of a neurobiological substrate controlling defensive behavior. It has been shown that a hypothalamic nucleus, the dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a defensive behavior related to panic attacks. The role played by the DMH in the organization of conditioned fear responses, however, is less clear. In the present study, we investigated the effects of reversible inactivation of the DMH with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape expression by male Wistar rats (approximately 280 g in weight) tested in the elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive response, has been associated with generalized anxiety disorder. Results showed that intra-DMH administration of the GABA A receptor agonist muscimol inhibited escape performance, suggesting an antipanic-like effect (P < 0.05), without changing inhibitory avoidance acquisition. Although a higher dose of muscimol (1.0 nmol/0.2 µL; N = 7) also altered locomotor activity in an open field when compared to control animals (0.2 µL saline; N = 13) (P < 0.05), the lower dose (0.5 nmol/0.2 µL; N = 12) of muscimol did not cause any motor impairment. These data corroborate previous evidence suggesting that the DMH is specifically involved in the modulation of escape. Dysfunction of this regulatory mechanism may be relevant in the genesis/maintenance of panic disorder.


Subject(s)
Anxiety Disorders/physiopathology , GABA-A Receptor Agonists/pharmacology , Hypothalamus/drug effects , Muscimol/pharmacology , Panic Disorder/etiology , Panic Disorder/physiopathology , Animals , Anxiety Disorders/etiology , Escape Reaction/drug effects , Hypothalamus/physiopathology , Male , Maze Learning/drug effects , Motor Activity/drug effects , Rats , Rats, Wistar
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