Participação dos receptores H2 histaminérgico, 5-Ht1a serotoninérgicos e Β-adrenérgico, do hipocampo, na facilitação da extinção da memória de medo condicionado ao contexto pela exposição a uma novidade

Abstract

Fear memories can lead to defensive behavior in response to threats, which can be modulated by different drugs or exposure to a novelty, for example. The histaminergic, serotonergic and adrenergic systems have receptors located in several areas in the brain, which are involved in the process of extinction memory. It is known that different processes can modulate the extinction memory, among them is the exposure to a novelty, which facilitates the formation of extinction memory. Here we investigate the participation of the H2-histaminergic, 5-HT1A serotonergic and β-adrenergic receptors of the hippocampus on the enhancement of extinction of fear memory by exposure to novelty. For this, male Wistar rats (300-330 g) were submitted to a stereotaxic surgery to implant guide cannula into the CA1 region of hippocampus. After 7 days of recovery, the animals were submitted to the experimental protocols (contextual fear conditioning with or without exposure to a novelty). The intra-CA1 infusion immediately after exposure to novelty or after extinction of the histaminergic H2 receptors agonist, Dimaprit (2,3 μg per side) or the antagonist, Ranitidine (17,5 μg per side) had no effect on the facilitation of extinction by exposure to novelty, suggesting that this receptor is not necessary in this process. It was also observed that the administration of 5-HT1A serotonergic receptor agonist, 8-OH-DPAT (6.25 μg per side) and of the blocker of β-adrenergic receptor, Timolol (1.0 μg per side) impaired the enhancement of the extinction memory induced by exposure to a novelty, thus suggesting that these receptors are involved in the process of facilitation of extinction by exposure to novelty. Thus, the results suggest that the 5-HT1A serotonergic and β-adrenergic receptors, but not H2-histaminergic receptors, play a role in the enhancement of extinction induced by novelty, indicating a complex regulation of the novelty effect by some, but not all, important neurotransmitter systems.