Os esteroides anabólicos androgênicos (EAA) são sintéticos derivados da testosterona que possuem propriedades anabólicas e androgênicas que promovem o aumento de massa muscular e o peso corporal. Esses fármacos vêm sendo utilizados em academias e centros de treinamento físico sem qualquer critério ou controle, representando um alto risco à saúde dos usuários, inclusive de ordem neurológica, como sintomas agressivos. Portanto, este estudo investigou o efeito dos EAAs sobre a distribuição de neurônios em áreas especificas do cérebro: a amígdala basolateral e central, bem como o impacto dessas drogas no comportamento de camundongos. Foram utilizados 40 camundongos machos da linhagem Swiss, do Biotério da Universidade Federal de Alfenas (Unifal- MG), divididos em 4 grupos (n=10): G1: Controle, G2: tratado com o anabolizante Deca durabolin®, G3: tratado com o anabolizante Durateston® e G4: tratado em ciclo com os dois anabolizantes, concomitantemente. Os camundongos foram tratados por dois meses, recebendo as doses dos EAAs e praticando natação. Após realizado o teste comportamental com labirinto em cruz elevado os camundongos foram eutanasiados, os cérebros retirados e armazenados em paraformaldeído a 4% 0,1M. Para a análise da estimativa da densidade de corpos celulares de neurônios foi utilizada a metodologia de contagem aleatória simples. O resultado da quantificação neuronal mostra que houve redução significativa de corpos celulares de neurônios nas regiões analisadas nos grupos tratados com anabolizantes em comparação com o grupo controle. A análise comportamental no labirinto em cruz elevado mostrou que os camundongos tratados com esteroides anabolizantes apresentaram um perfil ansiolítico quando comparados ao grupo controle. / The anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone, which possess anabolic and androgenic properties that promote increase in muscle mass and body weight. These drugs have been used in gyms and physical training centers without any criteria or control, representing a high health risk to users, including neurological, such as aggressive symptoms. Therefore, this study investigated the effects of AAS on neurons distribution act in specific brain areas: basolateral and central amygdala, as well as the impact of these drugs in mice behavior. 40 male mice of Swiss strain were used, from the Federal University of Alfenas (UNIFAL – MG) bioterium, divided into 4 groups (n=10): G1: Control, G2: treated with anabolic steroid Deca durabolin®, G3: treated with anabolic steroid Durateston® and G4: treated in cycle with both anabolic steroids, concomitantly. Mice were treated for two months, receiving the AAS doses and practicing swimming. After the behavioral test with elevated plus-maze was performed mice were euthanized, the brains were removed and stored in 4% paraformaldehyde 0,1M. For the analysis of the estimation of neuron cell bodies density, simple random counting method was used. The result of neuron quantification shows that there was significantly decrease of neuron cell bodies in the analyzed regions in groups treated with anabolic steroids, in comparison with the control group. Behavior analysis in elevated plus-maze showed that mice treated with anabolic steroids presented a anxiolytic profile when compared to the control group. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES

Ghrelin has been established as a hunger hormone because of its role in weight regulation and appetite stimulation. However, recent studies have uncovered a role for ghrelin in the modulation of negative emotional states like fear, anxiety and depression. The unusually high constitutive activity of the ghrelin receptor, growth hormone secretagogue receptor type 1a (GHSR1a) and its extensive ability to dimerize with other neuromodulatory receptors highlights the complexity of ghrelin receptor signaling. This led us to examine one of the essential constituents of this signaling mechanism. We exogenously administered GHSR1a into the basolateral complex of the amygdala (BLA), a region known to regulate negative emotional states. The Pavlovian fear conditioning paradigm was used to observe and compare the fear response of rats injected with GHSR1a and GFP to the fear response in rats injected with GFP alone. Our analyses revealed a significant attenuation of aversive memory recall in rats injected with GHSR1a and GFP, which suggests that increased ghrelin receptor signaling due to an overexpression of GHSR1a in the BLA impairs the consolidation and retrieval of conditioned fear memory. While other constituents of the ghrelin signaling mechanism remain to be investigated, our study provides an initial step in establishing ghrelin as a novel biomarker for stress-induced fear disorders.

In polarized epithelial cells, vectorial protein trafficking is important for transporting specific membrane proteins to generate distinct apical and basolateral membrane protein compositions. The Exocyst is a conserved hetero-octameric protein complex, which regulates different aspects of protein trafficking, including tethering of the Golgi-derived vesicles to target membranes. Two of the Exocyst subunits, Sec5 and Exo84, competitively bind to the small GTPases, RalA and RalB, in a GTP-dependent manner. Although Ral GTPases have been proposed to mediate assembly of Exocyst holocomplexes, we hypothesize that they actually serve to allosterically regulate Exocyst functions by promoting association or disassociation of additional factors. Previous studies have shown that active RalA, but not RalB, accelerated basolateral exocytosis of E-cadherin. In contrast, knockdown of RalB, but not RalA, disrupts endocytosis of E-cadherin. However, mechanisms by which association of Ral GTPases with Sec5 and Exo84 regulate basolateral protein trafficking remain unclear. Here we investigate roles of Ral GTPases and the Exocyst in regulating basolateral protein trafficking using Madin Darby canine kidney (MDCK) cells and RNA interference (RNAi) technology. We show that RalA, but not RalB, is required for basolateral exocytosis of vesicular stomatitis virus glycoprotein (VSV-G) in the MDCK cells. We combined immunofluorescent labeling and surface biotinylation assays to demonstrate that RalA regulates VSV-G trafficking through the distinct interactions with Sec5 and Exo84. We also show that a Ral-uncoupled Sec5 mutant, but not a Ral-uncoupled Exo84 mutant, inhibits E-cadherin exocytosis. These results suggested that RalA and the Exocyst are required for basolateral exocytosis, and that RalA-Sec5 and RalA-Exo84 interactions play different roles during this process. Our study may provide new insights into mechanisms regulating protein trafficking in epithelial cells, and potentially lead to development of new therapeutic targets for the treatment of diseases in which exocytosis is impaired, such as Polycystic kidney disease and diabetes.

Previous research investigating the neural circuitry underlying memory consolidation has primarily focused on single “nodes” in the circuit rather than the neural connections between brain regions, despite the likely importance of these connections in mediating different aspects or forms of memory. This focus has, in part, been due to technical limitations; however the advent of optogenetics has altered our capabilities in this regard, enabling optical control over neural pathways with temporal and spatial precision. The current set of experiments took advantage of optogenetics to control activity in specific pathways connecting brain regions in rats immediately after different kinds of learning. Chapter 2 first established the use of optogenetics to manipulate activity in the basolateral amygdala (BLA), which has been shown to modulate memory consolidation for a variety of types of learning likely through its connections to various downstream regions. Using a one-trial inhibitory avoidance task, a simple and robust fear learning paradigm, we found that both post-training stimulation and inhibition of BLA activity could enhance or impair later retention of the task, respectively. Enhancement was specific to stimulation using trains of 40, but not 20, Hz light pulses. Chapters 3 and 4 examined the projections from the BLA to the ventral hippocampus (VH) and medial entorhinal cortex (mEC) as the BLA’s ability to influence the consolidation for many types of memory is believed to be mediated through discrete projections to distinct brain regions. Indeed, the BLA innervates both structures, and prior studies suggest that the mEC and VH have distinct roles in memory processing related to contextual and nociceptive (footshock) learning, such as those involved in contextual fear conditioning (CFC). Optogenetic stimulation or inhibition of the BLA-VH or BLA-mEC pathway after training on a modified CFC task, in which the nociceptive or emotional stimulus (the footshock) and the context are separated, enabled experimental manipulations to selectively affect the consolidation for learning about one component and not the other. Optogenetic stimulation/inhibition was given to each candidate pathway immediately after the relevant training to determine its role in influencing consolidation for that component of the CFC learning. Chapter 3 results showed that stimulation of the BLA-VH pathway following footshock, but not context, training enhanced retention, an effect that was specific to trains of 40 Hz stimulation. Post-footshock photoinhibition of the same pathway impaired retention for the task. Similar investigations of the BLA-mEC pathway in Chapter 4 produced complementary findings. Post-context, but not footshock, stimulation of the pathway enhanced retention. In this particular case, only trains of 8 Hz stimulation were effective at enhancing retention. These results are the first, to our knowledge, to find that BLA inputs to different structures selectively modulate consolidation for different aspects of learning, thus enhancing our understanding of the neural connections underlying the consolidation of contextual fear conditioning and providing a critical foundation for future research.

Social stress is a prevalent factor in society that can cause or exacerbate neuropsychiatric disorders including depression and posttraumatic stress disorder. According to the National Institutes of Health, 6.9% of adults in this country currently suffer from depression, and 4.1% suffer from an anxiety disorder. Unfortunately, current treatments are ineffective in reducing or alleviating symptoms in a majority of these patients. Thus, it is critical to understand how social stress changes in brain and behavior so that we might develop alternative treatments. Brain derived neurotrophic factor (BDNF), which binds to tyrosine kinase B (TrkB) receptors, plays a role in fear learning and in behavioral responses to stress, although we do not currently know whether BDNF promotes or prevents these responses. The purpose of this project was to understand how BDNF alters brain and behavior in response to social stress using a model of social stress in Syrian hamsters, termed conditioned defeat (CD). CD refers to the marked increase in submissive and defensive behavior following social defeat. Specific Aim (SA) 1 tested the hypothesis that BDNF, via TrkB receptors, promotes CD learning. Instead, we found that BDNF and a selective TrkB receptor agonist reduced CD and that a TrkB receptor antagonist enhanced CD. SA 2 tested the hypothesis that the behavioral response observed following systemic administration of TrkB-active drugs is mediated via their action in specific nodes of the neural circuit underlying CD. Unfortunately, the vehicle in which these drugs are dissolved independently activates immediate early gene expression making interpretation of these data impossible. Finally, SA 3 tested the hypothesis that BDNF alters defeat-induced neural activation at least in part by acting in the medial prefrontal cortex (mPFC). We demonstrated that BNDF microinjected into the mPFC site-specifically altered defeat-induced neural activation in the CD neural circuit supporting this hypothesis. Overall, these data suggest that BDNF acts to prevent social stress-induced changes in behavior, at least in part via the basolateral amygdala and the mPFC, and that BDNF-active drugs might be a useful avenue to pursue to discover new treatments for patients that suffer from stress-related neuropsychiatric disorders.

Older adults tend to use strategies that differ from those used by young adults to solve decision-making tasks. MRI experiments suggest that altered strategy use during aging can be accompanied by a change in extent of activation of a given brain region, inter-hemispheric bilateralization or added brain structures. It has been suggested that these changes reflect compensation for less effective networks to enable optimal performance. One way that communication can be influenced within and between brain networks is through oscillatory events that help structure and synchronize incoming and outgoing information. It is unknown how aging impacts local oscillatory activity within the basolateral complex of the amygdala (BLA). The present study recorded local field potentials (LFPs) and single units in old and young rats during the performance of tasks that involve discrimination learning and probabilistic decision making. Wefound task-and age-specific increases in power selectively within the beta range (15-30 Hz). The increased beta power occurred after lever presses, as old animals reached the goal location. Periods of high-power beta developed over training days in the aged rats, and was greatest in early trials of a session. beta Power was also greater after pressing for the large reward option. These data suggest that aging of BLA networks results in strengthened synchrony of beta oscillations when older animals are learning or deciding between rewards of different size. Whether this increased synchrony reflects the neural basis of a compensatory strategy change of old animals in reward-based decision-making tasks, remains to be verified.

No description available.

A resposta comportamental de Imobilidade Tônica (IT) ocorre em situações de perigo intenso, e em situações inescapáveis, como por exemplo,o ataque de um predador. Esta resposta caracteriza-se por perda do reflexo de endireitamento e relativa falta de responsividade aos estímulos ambientais. Estudos consistentes tem demonstrado o envolvimento de distintas áreas encefálicas na modulação desta resposta, entre elas a substância cinzenta periaquedutal, o hipotálamo e a amígdala. Considerando a amígdala em particular, estudos mostraram o envolvimento dos receptores para o fator liberador de corticotropina (CRF) dos núcleos basolateral (BLA) e central (CeA) na modulação da resposta de IT em cobaias. De fato, nas últimas décadas, várias evidências sugerem que o CRF está intimamente correlacionado com comportamento emocional associado ao medo e à ansiedade. Embora seja claro o envolvimento de receptores CRF na modulação do medo, e especificamente na modulação da IT em cobaias, ainda não está esclarecido o envolvimento dos diferentes subtipos de receptores para CRF na modulação emocional. Desta forma, o objetivo deste trabalho foi investigar o envolvimento dos receptores específicos para o fator liberador de corticotropina, CRF1 e CRF2 dos núcleos basolateral (BLA) e central da amígdala (CeA) na modulação da resposta de IT em cobaias.Para atingir estes objetivos, grupos independentes de cobaias, com implante de cânulas-guias dirigidas para o BLA ou para o CeA foram avaliadas no teste de imobilidade tônica, antes e depois da administração dos antagonistas específicos para receptores CRF1 (CP-376395) ou para receptores CRF2 (Astressin 2B), ou depois da administração de CRF precedido ou não dos antagonistas CRF1 ou CRF2. Em adição, para avaliar se as drogas utilizadas alteraram a atividade locomotora, foi realizado o teste do campo aberto, por 5 minutos, após a administração dos antagonistas para receptores CRF1 (CP-376395) e CRF2 (Astressin 2B), em doses capazes de alterar a resposta de IT em cobaias, e de CRF precedido por antagonista CRF1 ou CRF2. Os resultados deste trabalho mostram que o bloqueio dos receptores CRF1 e CRF2 no BLA e no CeA reduziram a duração da resposta defensiva de imobilidade tônica (IT) em cobaias. Inversamente, a ativação destes receptores no BLA e no CeA aumentou o tempo de IT, demonstrado pela administração de CRF nestas regiões amigdalóides. Ainda, os antagonistas específicos para receptores CRF1 e CRF2 foram capazes de bloquear o aumento da duração da IT induzida pelo CRF administrado no mesmo sítio. Estes resultados sugerem que o efeito promovido pelo CRF no BLA e no CeA ocorre por atuação conjunta em receptores CRF1 e CRF2. Em adição, é importante ressaltar que as drogas, nas doses utilizadas neste estudo, não promoveram alteração da resposta motora, desde que não alteraram a atividade no teste do campo aberto, o que por si só, poderia alterar a resposta de IT. Assim, é possível que sugerir que o bloqueio específico de receptores CRF1 e CRF2 do BLA e do CeA promovem redução do medo e/ou da ansiedade, resultando em redução da resposta de IT em cobaias. / The tonic immobility response (TI ) occurs in inescapable situations of intense danger, such as the predator attack. This response is characterized by loss of righting reflex and the relative lack of responsiveness to environmental stimuli. Consistent studies have demonstrated the involvement of different brain areas to modulate this defensive behavior, including the periaqueductal gray matter, hypothalamus and amygdala. Whereas the amygdala in particular, studies have shown the involvement of receptors for corticotropin-releasing factor (CRF) of the central (CeA) and basolateral (BLA) nuclei os amygdala in TI modulating in guinea pigs. Indeed, in recent decades, several evidences suggest that CRF is closely correlated with emotional behavior associated with fear and anxiety. While it is clear the involvement of CRF receptors in the modulation of fear, and specifically in the modulation of TI, it is still unclear the involvement of different subtypes of CRF receptors in the emotional modulation. Thus, the aim of this study was to investigate the involvement of specific receptors for corticotropin-releasing factor, CRF1 and CRF2of BLA and of CeA in modulating the TI response in guinea pigs. To achieve these objectives, independent groups of guinea pigs were implanted with guide cannulae aimed for BLA or CeA were evaluated in the test of tonic immobility before and after the administration of specific antagonists of CRF1 receptors (CP- 376395) or CRF2 receptors (Astressin 2B), or after the administration of CRF preceded by CRF1or CRF2 antagonists, or CRF per se. In addition, to assess whether the drugs used altered locomotor activity, the open field test, for 5 minutes was performed after administration of antagonists for CRF1 receptors (CP- 376395) and CRF2 (Astressin 2B), at doses that alter the TI response in guinea pigs, and the CRF agonist preceded by CRF1 or CRF2. These results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA reduced the duration of the defensive response of tonic immobility (TI) in guinea pigs. In contrast, activation of these receptors in the BLA and CeA increased the TI duration, demonstrated by administration of CRF in these amygdaloid regions. Also, specific antagonists for CRF1 and CRF2 receptors were able to block the increase in the TI response induced by CRF administered in the same structure. These results suggest that the effect promoted by CRF in the BLA and CeA is by joint performance of CRF1 and CRF2 receptors. Additionally, it is important to note that the drugs, in the doses used in this study, did not promote change in the motor response, since it did not alter the activity in the open field test, which by itself could alter the TI response. Thus, it is possible to suggest that the specific blockade of CRF1 and CRF2 receptors in the BLA and CeA promote reduction of fear and/or anxiety, resulting in reduced TI response in guinea pigs.

A resposta comportamental de Imobilidade Tônica (IT) ocorre em situações de perigo intenso, e em situações inescapáveis, como por exemplo,o ataque de um predador. Esta resposta caracteriza-se por perda do reflexo de endireitamento e relativa falta de responsividade aos estímulos ambientais. Estudos consistentes tem demonstrado o envolvimento de distintas áreas encefálicas na modulação desta resposta, entre elas a substância cinzenta periaquedutal, o hipotálamo e a amígdala. Considerando a amígdala em particular, estudos mostraram o envolvimento dos receptores para o fator liberador de corticotropina (CRF) dos núcleos basolateral (BLA) e central (CeA) na modulação da resposta de IT em cobaias. De fato, nas últimas décadas, várias evidências sugerem que o CRF está intimamente correlacionado com comportamento emocional associado ao medo e à ansiedade. Embora seja claro o envolvimento de receptores CRF na modulação do medo, e especificamente na modulação da IT em cobaias, ainda não está esclarecido o envolvimento dos diferentes subtipos de receptores para CRF na modulação emocional. Desta forma, o objetivo deste trabalho foi investigar o envolvimento dos receptores específicos para o fator liberador de corticotropina, CRF1 e CRF2 dos núcleos basolateral (BLA) e central da amígdala (CeA) na modulação da resposta de IT em cobaias.Para atingir estes objetivos, grupos independentes de cobaias, com implante de cânulas-guias dirigidas para o BLA ou para o CeA foram avaliadas no teste de imobilidade tônica, antes e depois da administração dos antagonistas específicos para receptores CRF1 (CP-376395) ou para receptores CRF2 (Astressin 2B), ou depois da administração de CRF precedido ou não dos antagonistas CRF1 ou CRF2. Em adição, para avaliar se as drogas utilizadas alteraram a atividade locomotora, foi realizado o teste do campo aberto, por 5 minutos, após a administração dos antagonistas para receptores CRF1 (CP-376395) e CRF2 (Astressin 2B), em doses capazes de alterar a resposta de IT em cobaias, e de CRF precedido por antagonista CRF1 ou CRF2. Os resultados deste trabalho mostram que o bloqueio dos receptores CRF1 e CRF2 no BLA e no CeA reduziram a duração da resposta defensiva de imobilidade tônica (IT) em cobaias. Inversamente, a ativação destes receptores no BLA e no CeA aumentou o tempo de IT, demonstrado pela administração de CRF nestas regiões amigdalóides. Ainda, os antagonistas específicos para receptores CRF1 e CRF2 foram capazes de bloquear o aumento da duração da IT induzida pelo CRF administrado no mesmo sítio. Estes resultados sugerem que o efeito promovido pelo CRF no BLA e no CeA ocorre por atuação conjunta em receptores CRF1 e CRF2. Em adição, é importante ressaltar que as drogas, nas doses utilizadas neste estudo, não promoveram alteração da resposta motora, desde que não alteraram a atividade no teste do campo aberto, o que por si só, poderia alterar a resposta de IT. Assim, é possível que sugerir que o bloqueio específico de receptores CRF1 e CRF2 do BLA e do CeA promovem redução do medo e/ou da ansiedade, resultando em redução da resposta de IT em cobaias. / The tonic immobility response (TI ) occurs in inescapable situations of intense danger, such as the predator attack. This response is characterized by loss of righting reflex and the relative lack of responsiveness to environmental stimuli. Consistent studies have demonstrated the involvement of different brain areas to modulate this defensive behavior, including the periaqueductal gray matter, hypothalamus and amygdala. Whereas the amygdala in particular, studies have shown the involvement of receptors for corticotropin-releasing factor (CRF) of the central (CeA) and basolateral (BLA) nuclei os amygdala in TI modulating in guinea pigs. Indeed, in recent decades, several evidences suggest that CRF is closely correlated with emotional behavior associated with fear and anxiety. While it is clear the involvement of CRF receptors in the modulation of fear, and specifically in the modulation of TI, it is still unclear the involvement of different subtypes of CRF receptors in the emotional modulation. Thus, the aim of this study was to investigate the involvement of specific receptors for corticotropin-releasing factor, CRF1 and CRF2of BLA and of CeA in modulating the TI response in guinea pigs. To achieve these objectives, independent groups of guinea pigs were implanted with guide cannulae aimed for BLA or CeA were evaluated in the test of tonic immobility before and after the administration of specific antagonists of CRF1 receptors (CP- 376395) or CRF2 receptors (Astressin 2B), or after the administration of CRF preceded by CRF1or CRF2 antagonists, or CRF per se. In addition, to assess whether the drugs used altered locomotor activity, the open field test, for 5 minutes was performed after administration of antagonists for CRF1 receptors (CP- 376395) and CRF2 (Astressin 2B), at doses that alter the TI response in guinea pigs, and the CRF agonist preceded by CRF1 or CRF2. These results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA reduced the duration of the defensive response of tonic immobility (TI) in guinea pigs. In contrast, activation of these receptors in the BLA and CeA increased the TI duration, demonstrated by administration of CRF in these amygdaloid regions. Also, specific antagonists for CRF1 and CRF2 receptors were able to block the increase in the TI response induced by CRF administered in the same structure. These results suggest that the effect promoted by CRF in the BLA and CeA is by joint performance of CRF1 and CRF2 receptors. Additionally, it is important to note that the drugs, in the doses used in this study, did not promote change in the motor response, since it did not alter the activity in the open field test, which by itself could alter the TI response. Thus, it is possible to suggest that the specific blockade of CRF1 and CRF2 receptors in the BLA and CeA promote reduction of fear and/or anxiety, resulting in reduced TI response in guinea pigs.

Extensos dados na literatura têm assinalado a importância da serotonina (5-HT) na modulação de comportamentos de medo e ansiedade em roedores, a grande maioria utilizando ratos machos como sujeitos experimentais. No presente trabalho, foi analisada a influência da neurotransmissão 5-HT periférica e central sobre a expressão da resposta de medo condicionado e incondicionado de ratos machos e fêmeas, previamente selecionados pelo fenótipo como animais de baixa (BA) ou de alta (AA) reatividade emocional. Para este fim foi utilizado o teste do sobressalto potencializado pelo medo (SPM). A influência global e central de 5-HT foi avaliada pela utilização da administração sistêmica ou intraventricular aguda do inibidor irreversível da enzima triptofano hidroxilase PCPA (p-clorofenilalanina) nas doses de 200 mg/mL (i.p.) e 200 µg/5 µL (i.v.), ou através de infusões locais de 5-HT (10 nmol/0.2 µL) ou do agonista seletivo de receptores 5-HT1A 8-hidroxi-2-(di-n-propilamino)-tetralina (8-OH-DPAT) na dose de 0,3 µg/0.2 µL, diretamente em áreas encefálicas conhecidas por sua influência na modulação do medo e ansiedade a saber: o córtex pré-limbico (CPL), o núcleo basolateral da amígdala (BLA), e a substância cinzenta periaqueductal dorsal (SCPd) do mesencéfalo. As variáveis dependentes registradas foram a amplitude e a latência das respostas incondicionadas e condicionadas de sobressalto e a amplitude do SPM. / Extensive data in the literature have signaled the importance of serotonin (5-HT) on the modulation of fear and anxiety-like behaviors in rodents. In the present study, we have analyzed the influence of peripheral and central 5-HT neurotransmission on the expression of the conditioned and unconditioned fear, and on the fear-potentiated startle in male and female rats previously selected as low- (LA) or high-anxiety (HA). For this purpose, we used the fear-potentiated startle (FPS) test. The global and central influence of 5-HT was evaluated by using the acute systemic or intraventricular administration of the irreversible tryptophan hydroxylase inhibitor PCPA (p-chlorophenylalanine - 200 mg/mL i.p., or 200 µg/5 µL i.v.). Local effects were evaluated through local infusions of 5-HT itself (10 nmol/0.2 µL) or the selective 5-HT1A receptors agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT 0.3 µg/0.2 µL) in the prelimbic cortex (PrL), basolateral amygdala (BLA) or the dorsal periaqueductal gray (DPAG). These brain regions were chosen for the present study based on their great importance in the modulation and expression of conditioned and unconditioned fear. Dependent variables recorded were the amplitude and latency of unconditioned and conditioned fear, and fear-potentiated startle (FPS).