Research reportDorsal striatum mediation of cocaine-seeking after withdrawal from short or long daily access cocaine self-administration in rats

Accumulating evidence has suggested that prolonged use of cocaine may lead to progressive neuroadaptations proceeding from ventral to more dorsal areas of the corpus striatum. We have previously found that reversible inactivation of the dorsolateral caudate/putamen (dlCPu) significantly attenuated cocaine-seeking in rats following chronic cocaine self-administration and withdrawal. Since the cumulative amount of cocaine intake and the time course of withdrawal emergent patterns have been previously shown to alter subsequent cocaine-seeking, the current study investigated the role of the dlCPu in cocaine-seeking after differing access periods of cocaine self-administration and abstinence time points. Rats were catheterized and implanted with infusion cannulae in the dlCPu, trained on cocaine self-administration (0.2 mg/50 μl/infusion), and then allowed to self-administer cocaine for 1 or 6 h daily sessions. After the final session, animals underwent three separate tests of cocaine-seeking in the self-administration context at days 1, 14, and 60 of abstinence immediately following bilateral infusion of baclofen-muscimol or vehicle into the dlCPu. While inactivation of the dlCPu by baclofen-muscimol resulted in reduced cocaine-seeking in both groups, the degree of inhibited responding varied with access history and withdrawal time point. While these data support a role for dorsal striatal regions in cocaine-seeking, greater previous cocaine intake did not lead to a greater dependence on intact dlCPu function for cocaine-seeking after abstinence.

Research highlights▶ Prolonged use of cocaine leads to neuroadaptations in the dorsolateral caudate/putamen. ▶ The current study investigated the role of the dlCPu in cocaine-seeking after differing access periods of cocaine self-administration and abstinence time points. ▶ Inactivation of the dlCPu reduced cocaine-seeking that varied with prior cocaine access history and withdrawal time point.