Local pharmacological manipulations of prefrontal dopamine affect conflict behaviour in rats

Abstract

Several lines of research have implicated the prefrontal cortex (PFC) and its dopaminergic (DA) innervation in an animal's response to stress and anxiety. To extend these findings we evaluated the effects of bilateral infusions of DA drugs into the medial PFC of rats, in a modified conflict test, consisting of Reward, Conflict and Time-out components. In experiment 1, the effects of infusions of the DA receptor agonist apomorphine (APO) were compared to the effects of systemic injections of the same drug. APO infusions induced a dose-dependent decrease of responding in the Conflict component, indicative of an anxiogenic-like effect. However, response rates in the Reward component were simultaneously decreased, casting some doubt on the specificity of the effect. In comparison, i.p injections of APO in a second group of animals did not affect responding in the Conflict component, but dose-dependently decreased response rates during Time-out and Reward components. In experiment 2, we evaluated the effects of infusions of APO and the DA receptor antagonist cis-flupenthixol (FLU) into the medial PFC in the conflict test, and in one of its variants, the extinction of conflict test. Although both APO and FLU decreased response rates during Reward components, responding in the Conflict components of both tests was differentially affected. APO infusions decreased Conflict responses, the effect being more pronounced in the extinction of conflict test. In contrast, infusions of FLU increased responding in the Conflict components. The respective pro- and anti-conflict effects of APO and FLU infusions are in favour of a direct involvement of prefrontal DA in anxiety-related behavioural responses.