Using in vivo microdialysis, this study attempted to determine whether a neurochemical predisposition to self-administer cocaine could be identified. Estimated extracellular levels of dopamine and its metabolites were measured bilaterally in the mesocorticolimbic and nigrostriatal systems of naive rats that were subsequently trained to self-administer cocaine intravenously. There were several significant relationships between dopamine and dopamine metabolite (3,4-dihydroxyphenylacetic acid and homovanillic acid) levels and rates of cocaine self-administration during both acquisition and asymptotic phases of testing. Dopamine levels in the nucleus accumbens were non-monotonically related to rates of self-administration during both phases: low to moderate dopamine levels were positively correlated with self-administration rates whereas moderate to high dopamine levels were negative correlated with self-administration rates. Dopamine, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid) levels in the striatum were inversely correlated with self-administration rates during the acquisition phase. DOPAC and HVA levels in the left and right sides of the medial prefrontal cortex were positively and negatively correlated, respectively, with self-administration rates during the asymptotic phase; left/right asymmetrics in cortical metabolite levels were also correlated with asymptotic rates. There were no significant relationships between any neurochemical indices and rates of bar-pressing for water. These results suggest that the normal variability in drug seeking behavior is at least in part attributable to individual differences in the activity of brain dopamine systems.(ABSTRACT TRUNCATED AT 250 WORDS)