DOPAMINERGIC ANTAGONISM WITHIN THE NUCLEUS-ACCUMBENS OR THE AMYGDALA PRODUCES DIFFERENTIAL-EFFECTS ON INTRAVENOUS COCAINE SELF-ADMINISTRATION UNDER FIXED AND PROGRESSIVE RATIO SCHEDULES OF REINFORCEMENT

Bilateral intracerebral injections of the D1 receptor antagonist, SCH 23390, were administered into the nucleus accumbens (NACC) or amygdala (AMY) immediately prior to an i.v. cocaine self-administration sessio n. Injection into both sites produced a dose-dependent (0.1-2.0 mug/in jection) increase in the rate of cocaine self-administration under a f ixed ratio (FR) schedule of reinforcement (1.5 mg/kg/injection). Howev er, injection into the AMY produced a significantly greater increase i n rate of drug intake than within the NACC. In contrast, under a progr essive ratio (PR) schedule of cocaine reinforcement the D1 antagonist had very little effect within the AMY on break point (BP) but greatly reduced the BP following injection into the NACC. A locomotor activity study revealed that following systemic injection of cocaine (10 mg/kg i.p.), SCH 23390 (1.0 mug/injection site) significantly reduced activ ity to comparable levels following injection into either brain site. T his indicates that the dissociation of effects between the two neural sites within the cocaine self-administration paradigm does not appear to be due to greater locomotor reducing actions of the antagonist with in the NACC. These results demonstrate that a significant contribution is made by AMY dopamine to cocaine reinforcement mechanisms, which ap pears to be different to that of the NACC. Moreover, they suggest that FR and PR schedules may measure different aspects of cocaine's CNS ac tion which support self-administration behaviour.