AMPHETAMINE PRODUCES SENSITIZED INCREASES IN LOCOMOTION AND EXTRACELLULAR DOPAMINE PREFERENTIALLY IN THE NUCLEUS-ACCUMBENS SHELL OF RATS ADMINISTERED REPEATED COCAINE

Alterations in dopamine transmission in the nucleus accumbens, which i s composed of two anatomically distinct compartments termed the shell and core, contribute to the expression of cocaine-induced behavioral s ensitization. To test potential presynaptic components of behavioral s ensitization, the behavioral and neurochemical response to amphetamine administration in the accumbens shell and core was measured at early (days 1-3) and late (days 20-22) withdrawal in rats pretreated with sy stemic cocaine (15 mg/kg x 2 days, 30 mg/kg x 5 days) or saline. Behav ioral sensitization was observed at late, but not early withdrawal whe n amphetamine was microinjected into the nucleus accumbens shell of co caine-pretreated rats. There were no significant differences between c ocaine- and saline-pretreated animals when behavior was monitored afte r amphetamine injections into the core at either withdrawal period. Af ter both withdrawal periods, the amphetamine-induced increase in extra cellular dopamine was potentiated among cocaine-pretreated animals in the shell by the local administration of amphetamine (0.03, 0.3, 3.0 a nd 30 mu M through the dialysis probe). In the core at early withdrawa l there was tolerance to the amphetamine-induced increase in extracell ular dopamine in the cocaine group, whereas there was no difference be tween the repeated saline and cocaine groups at late withdrawal. In a second experiment designed to evaluate potential postsynaplic influenc es, the D-1 partial agonist, SKF-38393 (0.01 or 0.1 mu g/side), was mi croinjected into the nucleus accumbens core or shell regions after beh avioral sensitization to cocaine. Although there was a motor-stimulant effect of SKF-38393 at both withdrawal periods, there was no differen ce between rats pretreated with repeated cocaine or saline. Collective ly, these results demonstrate that the augmentation in dopamine transm ission in the nucleus accumbens that is associated with behavioral sen sitization is more robust in the shell than the core.