The effects of medial prefrontal cortex infusions of cocaine in a runway model of drug self-administration: evidence of reinforcing but not anxiogenic actions.

In previous work we have shown that rats running a straight alley for intravenous (i.v.) or intracerebroventricular (i.c.v.) injections of cocaine develop an ambivalence about entering the goal box that results from cocaine's mixed reinforcing and anxiogenic properties. What remains unclear is whether or not cocaine's opposing properties stem from actions on a common neuronal system or from dual actions on separate systems - one related to reward and another to anxiogenic responses. One way to address this question is to deliver cocaine into discrete brain areas as a means of assessing whether or not the positive and negative effects of the drug can be spatially dissociated. Given the putative role of mesocorticolimbic dopamine pathways in the mediation of cocaine-reinforced behavior, the current study examined the cocaine-seeking behavior of rats permitted to run an alley once each day for bilateral medial prefrontal cortex microinjections of cocaine (0.0, 12.5, 25 or 50 microg/0.5 microl per side) delivered upon goal-box entry. The results demonstrated that undrugged animals are highly motivated to seek medial prefrontal cortex cocaine without any evidence of negative or anxiogenic effects at any dose. These results are therefore consistent with suggestions of a medial prefrontal cortex involvement in the reinforcing actions of cocaine, and indicate that the dual and opposing actions of the drug can be dissociated and hence may be mediated by the drug's actions on separate neuronal systems.