Efeito do pentilenotetrazol e do midazolam na aquisição e na expressão da resposta defensiva de ratos submetidos ao condicionamento olfatório de medo

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Pavlovian fear conditioning or first-order fear conditioning has been widely used to study the neuroanatomical, cellular and molecular basis of fear. This paradigm occurs when an emotionally neutral stimulus is presented in conjunction with an aversive unconditioned stimulus (US). After one or several pairings the stimulus, previously neutral, acquires the aversive character becoming the first conditioned stimulus (CS1), capable to produce fear responses that typically occur only in the US presence. The aversive character of CS1 is able to act as US in the second-order fear conditioning due the CS1 acquired an aversive motivational value as relevant as the intrinsic (US). In this context, the magnitude of the US is one of the most important parameters in the study of fear conditioning because this magnitude determinates the learning rates and, indirectly, the second-order conditioning establishment. The US could be applied using exteroceptive (e.g. electric stimulus, predator odor etc.) or interoceptive sources (e.g. anxiogenic drugs effects). Here, we confirm the anxiogenic effect of the pentylenetetrazole (PTZ), GABAA antagonist, on 15 mg/kg allows using it as an interoceptive US in this study. Previous dados acquired in this laboratory, demonstrated that the olfactory fear conditioning (OFC) occurs after the association of 5 mild footshocks (exteroceptive US) with a neutral odor (coffee odor - CS1). In the present study, we observed that anxiogenic effect (interoceptive US) resulted from PTZ administration associated to only 3 mild footshocks was able to produce an increase in the contextual freezing time (in the presence of the CS1), similar to that observed in the animals paired with 5 footshocks not injected with PTZ. These data suggested that this association of stimulus (PTZ + 3 footshocks) were sufficient to promote the OFC. In the test of the hypothesis, we observed that this association increased the efficiency of the OFC, generating the greater defensive response. However, the defensive behavior exhibited by the subjects previously paired to the odor just with the anxiogenic effect of the PTZ (PTZ without footshocks) was also able to establish the OFC. Moreover, the results demonstrated that the aversive character acquired by the CS1 was sufficient to promote the second-order contextual fear conditioning, occurred in the re-exposure to the coffee odor (CS1) in the CS1 test session. The occurrence of the second conditioning was visualized by the defensive responses emitted in the re-exposure to the context (CS2) in the CS2 test session. In the aim of evaluate the GABAA agonist effect in the expression of the OFC and in the acquisition of the second-order fear conditioning, 0,5 mg/kg of MDZ was administrated previously the CS1 test session. The results demonstrate that MDZ counteract the expression of the conditioned fear responses in the re-exposure to CS1 in both paired groups (PTZ without footshocks and PTZ + 3 footshocks). In relation to the acquisition of the second-order fear conditioning, we observed the reversion in the fear responses only in the group previously paired to the odor with association of stimuli (PTZ + 3 footshocks). Together the results suggest that, beyond the anxiolytic-like effect, the MDZ generates a mnemonic effect in the acquisition of the second-order fear conditioning according to the strength of the first conditioning establishment.

ASSUNTO(S)

pentilenotetrazol farmacologia midazolam medo

ACESSO AO ARTIGO

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