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The neuropeptide PACAP, acting as a co-transmitter, increases neuronal excitability, which may enhance anxiety and arousal associated with threat conveyed by multiple sensory modalities. The distribution of neurons expressing PACAP and its receptor, PAC1, throughout the mouse nervous system was determined, in register with expression of glutamatergic and GABAergic neuronal markers, to develop a coherent chemoanatomical picture of PACAP role in brain motor responses to sensory input. A circuit role for PACAP was tested by observing Fos activation of brain neurons after olfactory threat cue in wild-type and PACAP knockout mice. Neuronal activation and behavioral response, were blunted in PACAP knock-out mice, accompanied by sharply downregulated vesicular transporter expression in both GABAergic and glutamatergic neurons expressing PACAP and its receptor. This report signals a new perspective on the role of neuropeptide signaling in supporting excitatory and inhibitory neurotransmission in the nervous system within functionally coherent polysynaptic circuits.

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Several fish species trigger defensive behavioral responses when exposed to chemical cues that indicate predation risk. In these situations, physiological adjustments are also necessary to prepare the organism for a defensive response and increase survival odds. Chemical cues may be derived from predator odor or injured conspecifics. However, little is known about the effects of both cues combined. Therefore, our study evaluated the combined effects of predator odor (PO) and conspecific alarm substance (CAS) on the anti-predatory responses of the pearl cichlid (Geophagus brasiliensis). We set 4 experimental conditions 1) PO + CAS; 2) PO + Distilled Water (DW); 3) DW + CAS; and 4) DW + DW (negative control). Fish exposed to DW + CAS had values of ventilation rate and feeding latency significantly higher than when exposed to the other conditions, which yielded similar responses for both variables. Our data show that the combination of PO + CAS interfered with pearl cichlid behavior and physiology since it abolished CAS defensive responses. These results show that CAS plays an important role on the defensive responses of pearl cichlids, while PO does not, given that fish did not respond to PO by itself. Our findings point to different cue-specific strategies in pearl cichlids when dealing with different chemical cues that indicate predation risk.

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The recognition of chemical information indicating the presence of a predator is very important for prey survival. In this study we tested antipredator behavioral response of juvenile silver catfish (Rhamdia quelen) against predator odor released by two different potential predators, Hoplias malabaricus and the snake Helicops infrataeniatus, and alarm cues and disturbance cues released by conspecifics and by non-predator species, Megaleporinus obtusidens and Astyanax lacustris. We used juvenile catfish that were naive to predators. The trials consisted of a 10-min prestimulus and a 10-min post-stimulus observation period. The behavioral response displayed by silver catfish exposed to alarm cues comprised a decrease in shelter use and an increase in locomotion, and also a longer latency period before feeding. Our results showed that juvenile silver catfish can perceive chemical cues released by predators, heterospecifics and conspecifics.(AU)

O reconhecimento das informações químicas indicando a presença de predadores é muito importante para a sobrevivência da presa. Neste estudo foi testada a resposta comportamental anti-predação de juvenis de jundiás (Rhamdia quelen) a substâncias liberadas por dois predadores potenciais, Hoplias malabaricus e a cobra Helicops infrataeniatus, e substâncias de alarme liberadas por conspecíficos e pelas espécies não predadoras Megaleporinus obtusidens e Astyanax lacustris. Foram usados juvenis de jundiá que não possuíam nenhum contato prévio com predadores. Os testes consistiram em observações de períodos de 10 minutos pré estímulo e 10 minutos pós estímulo. As respostas comportamentais apresentadas pelos jundiás expostos às substâncias de alarme consistiram em diminuição no uso do abrigo, aumento na locomoção e também um longo período de latência antes de ingerir o alimento. Os resultados demonstram que juvenis de jundiá percebem substâncias químicas liberadas por predadores, heterospecíficos e conspecíficos.(AU)

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The recognition of chemical information indicating the presence of a predator is very important for prey survival. In this study we tested antipredator behavioral response of juvenile silver catfish (Rhamdia quelen) against predator odor released by two different potential predators, Hoplias malabaricus and the snake Helicops infrataeniatus, and alarm cues and disturbance cues released by conspecifics and by non-predator species, Megaleporinus obtusidens and Astyanax lacustris. We used juvenile catfish that were naive to predators. The trials consisted of a 10-min prestimulus and a 10-min post-stimulus observation period. The behavioral response displayed by silver catfish exposed to alarm cues comprised a decrease in shelter use and an increase in locomotion, and also a longer latency period before feeding. Our results showed that juvenile silver catfish can perceive chemical cues released by predators, heterospecifics and conspecifics.(AU)

O reconhecimento das informações químicas indicando a presença de predadores é muito importante para a sobrevivência da presa. Neste estudo foi testada a resposta comportamental anti-predação de juvenis de jundiás (Rhamdia quelen) a substâncias liberadas por dois predadores potenciais, Hoplias malabaricus e a cobra Helicops infrataeniatus, e substâncias de alarme liberadas por conspecíficos e pelas espécies não predadoras Megaleporinus obtusidens e Astyanax lacustris. Foram usados juvenis de jundiá que não possuíam nenhum contato prévio com predadores. Os testes consistiram em observações de períodos de 10 minutos pré estímulo e 10 minutos pós estímulo. As respostas comportamentais apresentadas pelos jundiás expostos às substâncias de alarme consistiram em diminuição no uso do abrigo, aumento na locomoção e também um longo período de latência antes de ingerir o alimento. Os resultados demonstram que juvenis de jundiá percebem substâncias químicas liberadas por predadores, heterospecíficos e conspecíficos.(AU)

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The dorsolateral region of the midbrain periaqueductal gray (dlPAG) modulates both innate and conditioned fear responses. However, the contribution of the rostrocaudal portions of the dlPAG to defense reactions and aversive memories remains unclear. Here, we sought to investigate the effects of N-methyl-d-aspartate (NMDA) receptor blockade within rostral or caudal dlPAG of rats exposed to innate and learned fear to cat odor. For this, adult male Wistar rats were microinjected with the NMDA antagonist D-2-amino-5-phosphono-pentanoate (AP5; 3 or 6nmol/0.2µl) into the rostral or caudal dlPAG before and after the exposure to the cat odor or to the context paired with the predator odor. The results demonstrated that cat odor exposure induced unconditioned defensive behaviors as well as contextual fear. AP5 microinjected in the rostral dlPAG reduced the defensive responses to cat odor and impaired the acquisition, but not consolidation of contextual fear. On the other hand, AP5 infused within the caudal dlPAG promoted long-lasting reduction of contextual fear expression. Altogether, our data suggest that NMDA receptors mediate a functional dichotomy in the rostrocaudal axis of dlPAG regulating unconditioned and conditioned defensive reactions to predatory cues.

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Studies from the last two decades have pointed to multiple mechanisms of fear. For responding to predators, there is a group of highly interconnected hypothalamic nuclei formed by the anterior hypothalamic nucleus, the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus­the predator-responsive hypothalamic circuit. This circuit expresses Fos in response to predator presence or its odor. Lesion of any component of this system blocks or reduces the expression of fear and consequently defensive behavior when faced with a predator or its cue. However, most of the knowledge about that circuit has been obtained using the rat as a model of prey and the cat as a source of predator cues. In the present study, we exposed mice to strong cat or snake odors, two known mice predators, and then we used the rat exposure test (RET) to study their behavior when confronted with the same predator's odor. Our data point to a differential response of mice exposed to these odors. When Swiss mice were exposed to the cat odor, they show defensive behavior and the predator-responsive hypothalamic circuit expressed Fos. The opposite was seen when they faced snake's odor. The acute odor exposure was not sufficient to activate the mouse predator-responsive hypothalamic circuit and the mice acted like they were not in a stressful situation, showing almost no sign of fear or defensive posture. This leads us to the conclusion that not all the predator cues are sufficient to activate the predator-responsive hypothalamic circuit of mice and that their response depends on the danger that these predators represent in the natural history of the prey.

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Different types of predator odors engage elements of the hypothalamic predator-responsive circuit, which has been largely investigated in studies using cat odor exposure. Studies using cat odor have led to detailed mapping of the neural sites involved in innate and contextual fear responses. Here, we reviewed three lines of work examining the dynamics of the neural systems that organize innate and learned fear responses to cat odor. In the first section, we explored the neural systems involved in innate fear responses and in the acquisition and expression of fear conditioning to cat odor, with a particular emphasis on the role of the dorsal premammillary nucleus (PMd) and the dorsolateral periaqueductal gray (PAGdl), which are key sites that influence innate fear and contextual conditioning. In the second section, we reviewed how chemical stimulation of the PMd and PAGdl may serve as a useful unconditioned stimulus in an olfactory fear conditioning paradigm; these experiments provide an interesting perspective for the understanding of learned fear to predator odor. Finally, in the third section, we explored the fact that neutral odors that acquire an aversive valence in a shock-paired conditioning paradigm may mimic predator odor and mobilize elements of the hypothalamic predator-responsive circuit.

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Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

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