Dopaminergic mechanisms in the conditioned and unconditioned fear as assessed by the two-way avoidance and light switch-off tests

Abstract

The involvement of dopaminergic mechanisms in fear and anxiety is still unclear. Behavioral studies aimed to disclose the involvement of dopamine in anxiety have reported anxiolytic-like, anxiogenic-like and lack of effects with the use of dopaminergic agonists and antagonists in animal models of anxiety. This work was an attempt to contribute to this field by providing evidence that these discrepancies may be due to the kind of aversive situation the animals experience in these models. The present study examined the effects of a dopaminergic agonist apomorphine, a dopaminergic D(1) antagonist SCH 23390 and a D(2) receptor antagonist sulpiride on the two-way avoidance response test (CAR) and on the switch-off responses to light (SOR). In both tests, learning was assessed by the performance of the animals across four blocks of 10 trials in which light was paired to footshocks (CAR) or only light was presented to the animals (SOR). The obtained data show that rats learn to make a shuttling response to avoid the shock in the CAR test and maintain a regular pace of switch-off responses in the SOR. While sulpiride and SCH 23390 administrations prevented learning of the avoidance responses, apomorphine injections produced a dose-dependent enhancement in the conditioned learning in the CAR test. The number of escape responses was unchanged by these drugs. In the light-induced switch-off test, apomorphine reduced the number of switch-off responses whereas sulpiride increased these responses. These findings suggest that the involvement of dopaminergic mechanisms in threatening situations depends on the nature of the aversive stimulus. Activation of D(1) and D(2) receptors seems to be implicated in the heightened aversiveness to conditioned stressful situations, as assessed by the CAR test. Thus, blockade of D(1) and D(2) receptors may be necessary for attenuating the aversiveness triggered by these conditioned fear stimuli. In contrast, mechanisms mediated by D(2) receptors seem to be involved in the setting up of adaptive responses to innate fear reactions. Therefore, the signal of the modulatory dopaminergic mechanisms on defensive behavior will depend on the type of emotional stimuli triggering the coping reaction.