We have previously reported time-dependent and dose-dependent changes in the rat dopaminergic receptor system following chronic administration of cocaine (upregulation of cocaine, D1, and DA-uptake sites). We have now evaluated the effects of chronic cocaine exposure on the central catecholamine/indolamine neurotransmitter systems. Groups of rats were injected with cocaine (15 mg/kg, i.p., b.i.d.) or saline for 1, 3, 7, 14 or 21 days. Cortical and striatal tissues were analyzed for norepinephrine, dopamine, serotonin and their primary metabolites using a HPLC-ECD method. Chronic administration of cocaine did not change the cortical and striatal concentrations of the neurotransmitters under study; except, for a transient increase in the cortical MHPG concentration on day 3. These results suggest that changes in the dopaminergic receptor system following chronic cocaine exposure are not due to changes in the neurotransmitter concentrations.