Envolvimento de mecanismos dopaminérgicos na expressão do medo condicionado contextual em ratos

Abstract

It is well established that experiences that generate fear reactions are practically unforgettable and that aversive conditioning raises several defensive responses such as freezing, which is an index of fear in rodents. Several studies have pointed to the existence of a relationship between changes in dopaminergic neurotransmission and aversive states. However, there are conflicting results in the literature with the use of dopaminergic drugs in different animal models of anxiety. Thus, further investigations should be conducted to evaluate the importance of dopaminergic modulation of aversive states. The aim of the present study was to evaluate the involvement of dopaminergic neurotransmission in the expression of contextual conditioned fear in rats. Initially, we evaluated the effects of intraperitoneal injections of D1 and D2 receptors agonists (SKF 38393 and quinpirole) and antagonists (SCH 23390 and sulpiride) in the expression of contextual conditioned fear by measuring the time of freezing response of the animals. The motor activity was evaluated in the open field test. The results indicate that the D2 receptors, but not D1 receptors, are involved in the expression of contextual conditioned fear, since administration of quinpirole and sulpiride, but not SCH 23390 and SKF 38393, decreased conditioned freezing to the context. There were no changes in motor activity of animals. Based on these results it was hypothesized that quinpirole and sulpiride probably acted on presynaptic and postsynaptic D2 receptors, respectively, leading to a decrease of dopaminergic neurotransmission in both cases. To test this hypothesis, microinjections of quinpirole were performed into the ventral tegmental area (VTA). The results show a decrease in the expression of conditioned freezing, indicating that the effects obtained with the intraperitoneal administration of the dopamine D2 receptor agonist is probably due to its action in the VTA. Therefore, dopaminergic mechanisms in the VTA seem to be important in the modulation of conditioned fear responses and activation of this structure appears to take place during the fear memory following the context aversive conditioning.