CONDITIONED COCAINE-INDUCED HYPERACTIVITY - AN ASSOCIATION WITH INCREASED MEDIAL PREFRONTAL CORTEX SEROTONIN

Two sets of contextual stimuli, only one of which was associated with drug treatment, were employed in a new paradigm to assess the conditioned effects of ten cocaine (20 mg/kg) treatments on motoric behavior. Two matched groups of Sprague-Dawley rats were sequentially placed into two similar but distinct test compartments. The drug treatment was administered immediately prior to placement into the second test compartment in one group (paired group) but 2 h later in the other group (unpaired group). Changes in the non drug behavioral baseline were assessed in the non drug compartment immediately prior to each drug treatment and provided the referent baseline for determining stimulus specificity of the observed behavioral effects in the drug compartment. Both groups had equivalent activity levels in the non-drug compartment. In the drug compartment, however, the paired group showed an overall cocaine stimulant effect expressed as a marked increase in distance traversed in the drug box. Additionally, the repeated cocaine treatment induced a conditioned drug effect as revealed by the higher level of motor activity in the paired compared to the unpaired treatment group exclusively in the drug compartment in two post-treatment non-drug tests for conditioning after 1-day and 21-day withdrawal and non-testing intervals. The biochemical assay results showed no significant group differences in DA and dopamine metabolites, DOPAC, HVA and 3-MT, in striatal, limbic or cortical tissue. No differences were observed either in NE or plasma corticosterone levels. Importantly, the analysis for serotonin revealed higher levels of 5-HT and 5-HIAA selectively in the prefrontal cortex. These results suggest a role for the prefrontal cortex in the mediation of conditioned stimulant effects of cocaine.