EFFECT OF 6-HYDROXYDOPAMINE LESIONS OF THE MEDIAL PREFRONTAL CORTEX ON INTRAVENOUS COCAINE SELF-ADMINISTRATION UNDER A PROGRESSIVE RATIO SCHEDULE OF REINFORCEMENT

Rats were trained to self-administer intravenous cocaine under a progr essive ratio (PR) schedule of reinforcement. Under this schedule, an i ncreasing number of lever responses had to be made to obtain each subs equent reinforcement (1.5 mg/kg per injection). Once stable responding was achieved with this schedule, bilateral 6-hydroxydopamine (6-OHDA) or vehicle-only injections were delivered into the medial prefrontal cortex (mPFC). Following recovery from surgery, the animals were given access to cocaine under the PR schedule. The effect of the lesion on self-administration behaviour was examined at various doses of cocaine (0.09-1.5 mg/kg per injection). 6-OHDA lesions of the mPFC had no eff ect on self-administration behaviour at the higher unit doses of cocai ne. However, at the lower doses (0.09 and 0.19 mg/kg per injection), t he lesion caused a significant increase in break point (BP), the numbe r of responses made to obtain the last reinforcement of a self-adminis tration session. The neurochemical results showed a significant reduct ion (57%) in mPFC levels of dopamine (DA) and 3,4-dihydroxyphenylaceti c acid (DOPAC) (53%), with no changes in noradrenaline or serotonin le vels. In contrast, the lesion caused no changes in DA or DOPAC levels in the nucleus accumbens (NACC) or striatum. These results indicate th at the DAergic innervation of the mPFC cortex has a role in cocaine se lf-administration behaviour; however, whether this role is contingent on NACC DA function remains to be elucidated.