Institute Neurociencias e Comportamento INeC

Ribeirão Preto, Brazil

Institute Neurociencias e Comportamento INeC

Ribeirão Preto, Brazil

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Coimbra N.C.,University of Sao Paulo | Coimbra N.C.,Institute Neurociencias e Comportamento INeC | Paschoalin-Maurin T.,University of Sao Paulo | Bassi G.S.,University of Sao Paulo | And 13 more authors.
Revista Brasileira de Psiquiatria | Year: 2017

Objective:To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors’ research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. Results: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Conclusions: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs. © 2017, Associacao Brasileira de Psiquiatria. All rights reserved.


Almeida Pv.G.,University of Sao Paulo | Trovo M.C.,University of Sao Paulo | Tokumoto A.M.,University of Sao Paulo | Pereira A.C.,University of Sao Paulo | And 3 more authors.
Journal of Psychopharmacology | Year: 2013

Despite the intense research on the neurobiology of stress, the role of serotonin (5-HT)1A receptors still remains to be elucidated. In the hippocampus, post-synaptic 5-HT1A receptors activation induces anxiolytic effects in animals previously exposed to stressful situations. However, little is known about somatodendritic 5-HT1A receptors in the median raphe nucleus (MRN). Therefore, the aim of this study was to investigate the role of 5-HT1A receptors located in the MRN in rats exposed to forced swim stress. After recovering from surgery, rats were forced to swim for 15 min in a cylinder. Intra-MRN injections of saline, 8-OH-DPAT (3 nmol/0.2 μL) and/or WAY-100635 (0.3 nmol/0.2 μL) were performed immediately before or after pre-exposure or 24 h later (immediately before test). Non-stressed rats received the same treatment 24 h or 10 min before test. Our data showed that 8-OH-DPAT increased latency to display immobility while decreasing time spent immobile in almost all experimental conditions. These effects were not prevented by previous treatment with WAY-100635. No effects of different treatments were described in non-stressed animals. Taken together, our data suggest that in addition to activation of 5-HT1A, 5-HT7 receptors may also be involved in the behavioural consequences of exposure to swim stress. © The Author(s) 2013.


De Oliveira A.R.,University of Sao Paulo | De Oliveira A.R.,Institute Neurociencias e Comportamento INeC | Reimer A.E.,University of Sao Paulo | Reimer A.E.,Institute Neurociencias e Comportamento INeC | And 2 more authors.
Psychoneuroendocrinology | Year: 2014

Despite the recognized involvement of corticosteroids in the modulation of emotional behavior, the specific role of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the expression of conditioned fear responses is still open to investigation. The present study sought to clarify the involvement of both types of corticosteroid receptors in two different brain regions - the ventral tegmental area (VTA) and the basolateral amygdala complex (BLA) - on the expression of conditioned fear. The first experiment assessed the effects of intra-VTA or intra-BLA administration of spironolactone (MR antagonist) or mifepristone (GR antagonist) on the expression of conditioned freezing to a light-CS and on motor performance in the open-field test. Intra-VTA spironolactone, but not mifepristone, attenuated the expression of the conditioned freezing response whereas intra-BLA spironolactone or mifepristone had no significant effects. These treatments did not affect motor performance in the open-field test. Since dopamine is released in the BLA from the VTA during the expression of conditioned fear, the anxiolytic-like effect of decreased corticosteroid activity in the first experiment could be associated with changes in dopaminergic neurotransmission. The second experiment, using in vivo microdialysis, investigated the role of MRs in the VTA on dopamine levels in the BLA during the expression of conditioned fear. Blocking MRs locally in the VTA with spironolactone reduced dopamine efflux in the BLA and decreased the expression of conditioned freezing in response to the CS. Taken together, the data indicate that corticosterone, acting locally on MRs in the VTA, stimulates dopamine efflux in the BLA, which facilitates the expression of conditioned freezing to a light-CS. © 2014 Elsevier Ltd.


Gonzaga N.A.,University of Sao Paulo | Batistela M.R.,University of Sao Paulo | Padovan D.,University of Sao Paulo | de Martinis B.S.,University of Sao Paulo | And 5 more authors.
Alcohol | Year: 2016

Nitric oxide (NO) mediated transmission in the dorsal raphe nucleus (DRN) has been shown to be involved in the modulation of anxiety-like behaviors. We investigated whether inhibition of nitric oxide synthase (NOS) in the DRN would prevent anxiety-like behavior induced by ethanol withdrawal. Male Wistar rats were treated with ethanol 2-6% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats with a guide cannula aimed at the DRN received intra-DRN injections of the non-selective NOS inhibitor NG-nitro-. l-arginine methyl ester (. l-NAME), selective neuronal NOS (nNOS) inhibitor N(ω)-propyl-. l-arginine (NPLA), or selective inhibitor of inducible NOS (iNOS) N-([3-(aminomethyl)phenyl] methyl) ethanimidamidedihydrochloride (1400W). Five minutes later, the animals were tested in the elevated plus maze (EPM). Plasma ethanol levels were determined by gas chromatography. There was a reduction in plasma ethanol levels 48 h after ethanol withdrawal. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the EPM with no change in the exploration of enclosed arms. Intra-DRN treatment with l-NAME (100 nmoles/0.2 μL) and 1400W (1 nmol/0.2 μL), but not NPLA (10 nmoles/0.2 μL) in the DRN attenuated the decrease in the exploration of the open arms of the EPM induced by ethanol withdrawal. The major new finding of the present study is that iNOS in the DRN plays a role in the anxiety-like behavior induced by ethanol withdrawal. © 2016 Elsevier Inc.


Reis F.M.C.V.,University of Ribeirão Preto | Reis F.M.C.V.,Institute Neurociencias e Comportamento INeC | Pestana-Oliveira N.,University of Sao Paulo | Leite C.M.,University of Sao Paulo | And 7 more authors.
Psychoneuroendocrinology | Year: 2014

Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80. ±. 5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5. min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes. © 2014 Elsevier Ltd.


De Paula Soares-Rachetti V.,Federal University of Rio Grande do Norte | De Sousa Pinto I.A.,Federal University of Rio Grande do Norte | Santos R.O.,Federal University of Rio Grande do Norte | Andre E.,Federal University of Paraná | And 3 more authors.
Journal of Psychopharmacology | Year: 2016

Anxiety behavior in female Wistar rats was assessed at different stages of the estrous cycle using the elevated plus maze (EPM). No differences were observed at any cycle stage. Pretreatment with diazepam (1 mg kg-1 intraperitoneal (i.p.)) 30 min before testing produced an anxiolytic effect (significant increase in percentage of time in the open arms compared to control group in the same cycle phase) in animals in proestrus, estrus, and early diestrus but had no effect in rats in late diestrus. Locomotor activity (total arm entries) was unchanged at any cycle phase. When rats in the late diestrus phase were pretreated with the selective serotonin reuptake inhibitor fluoxetine (1.75 mg kg-1 i.p. on the afternoon of early diestrus and again in the morning of late diestrus) diazepam produced an anxiolytic effect (increase percentage time in the open arms). This dose is sufficient to raise brain allopregnanolone concentration without affecting 5-hydroxytryptamine (5-HT) systems. We propose that insensitivity to diazepam in late diestrus is due to increased expression of benzodiazepine insensitive α4 subunit-containing gamma-aminobutyric acid A (GABAA) receptors triggered by a sharp decrease in brain allopregnanolone concentration. Pretreatment with fluoxetine to raise brain allopregnanolone concentration during late diestrus prevents the withdrawal effect. © British Association for Psychopharmacology.


PubMed | Institute Neurociencias e Comportamento INeC
Type: Journal Article | Journal: Stress (Amsterdam, Netherlands) | Year: 2012

The extent to which the hypothalamic-pituitary-adrenal axis is activated by short-term and long-term consequences of stress is still open to investigation. This study aimed to determine (i) the correlation between plasma corticosterone and exploratory behavior exhibited by rats subjected to the elevated plus maze (EPM) following different periods of social isolation, (ii) the effects of the corticosterone synthesis blocker, metyrapone, on the behavioral consequences of isolation, and (iii) whether corticosterone produces its effects through an action on the anterior cingulate cortex, area 1 (Cg1). Rats were subjected to 30-min, 2-h, 24-h, or 7-day isolation periods before EPM exposure and plasma corticosterone assessments. Isolation for longer periods of time produced greater anxiogenic-like effects on the EPM. However, stretched attend posture (SAP) and plasma corticosterone concentrations were increased significantly after 30min of isolation. Among all of the behavioral categories measured in the EPM, only SAP positively correlated with plasma corticosterone. Metyrapone injected prior to the 24h isolation period reversed the anxiogenic effects of isolation. Moreover, corticosterone injected into the Cg1 produced a selective increase in SAP. These findings indicate that risk assessment behavior induced by the action of corticosterone on Cg1 neurons initiates a cascade of defensive responses during exposure to stressors.

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