A comparative study on the effects of the benzodiazepine midazolam and the dopamine agents, apomorphine and sulpiride, on rat behavior in the two-way avoidance test

In recent years, studies in behavioral pharmacology have shown the involvement of dopaminergic mechanisms in avoidance behavior as assessed by the two-way active avoidance test (CAR). Changes in dopaminergic transmission also occur in response to particularly threatening challenges. However, studies on the effects of benzodiazepine (BZD) drugs in this test are still unclear. Given the interplay of dopamine and other neurotransmitters in the neurobiology of anxiety and schizophrenia the aim of this work was to evaluate the effects of systemic administration of midazolam, the dopaminergic agonist apomorphine, and the D₂ receptor antagonist sulpiride using the CAR, a test that shows good sensitivity to typical neuroleptic drugs. Whereas midazolam did not alter the avoidance response, apomorphine increased and sulpiride reduced them in this test. Escape was not affected by any drug treatments. Heightened avoidance was not associated with the increased motor activity caused by apomorphine. In contrast with the benzodiazepine midazolam, activation of post-synaptic D₂ receptors with apomorphine facilitates, whereas the D₂ receptor antagonism with sulpiride inhibited the acquisition of the avoidance behavior. Together, these results bring additional evidence for a role of D₂ mechanisms in the acquisition of the active avoidance.