Dopamine D2 receptors modulate the expression of contextual conditioned fear: role of the ventral tegmental area and the basolateral amygdala

Abstract

Although dopaminergic systems are more commonly associated with the reinforcing effects of various stimuli, numerous reports have demonstrated a relationship between changes in dopaminergic transmission and aversive situations. In the present study, we examined the involvement of D1-like and D2-like receptors in the expression of conditioned freezing using the context as the conditioned stimulus. Intraperitoneal injections of the D1 agonist SKF38393 or the D1 antagonist SCH23390 did not change the conditioned freezing in rats subjected to the contextual fear paradigm. In contrast, intraperitoneal injections of the D2 agonist quinpirole and the D2 antagonist sulpiride caused a significant dose-dependent reduction in the expression of contextual conditioned freezing. As these data may reflect that the systemic manipulations acted on dopaminergic receptors in different brain areas, the effects of administration of quinpirole and sulpiride into the ventral tegmental area (VTA) and the basolateral amygdala complex (BLA) on the expression of contextual conditioned freezing were also evaluated. Intra-VTA quinpirole and intra-BLA sulpiride injections reduced the conditioned freezing response; intra-VTA sulpiride and intra-BLA quinpirole injections had no significant effects. These data suggest that D2-like receptors, but not D1-like receptors, play an important role in the expression of contextual conditioned freezing. Quinpirole may act at D2 presynaptic receptors located in the VTA, decreasing dopamine levels in the terminal fields of the mesolimbic pathway. The effects of sulpiride, in contrast, appear to be triggered by an action on postsynaptic dopaminergic receptors located in the BLA. However, it cannot be totally excluded that the injected solutions did not also affect neighboring amygdalar regions. Together with previous findings, the present data suggest the need to consider dopaminergic mechanisms in the mesolimbic circuit as novel targets for the pharmacological treatment of fear-related disorders, especially post-traumatic stress disorder.