THE PERSISTENCE OF BEHAVIORAL SENSITIZATION TO COCAINE PARALLELS ENHANCED INHIBITION OF NUCLEUS-ACCUMBENS NEURONS

The mesoaccumbens dopamine system is intricately involved in the locom otor stimulation produced by cocaine and sensitization of this effect following repeated cocaine administration. The mechanisms responsible for the expression of sensitized locomotion appear to involve alterati ons in both presynaptic (increased dopamine release) and postsynaptic (increased responsiveness of dopamine D1 receptors) aspects of dopamin e neurotransmission within the nucleus accumbens. The present experime nts used behavioral and single-cell electrophysiological techniques to determine the persistence of sensitization and of enhanced postsynapt ic responses to cocaine within the nucleus accumbens following various periods of withdrawal from repeated cocaine treatment (10 mg/kg i.p., twice daily, 14 d). Behavioral sensitization to the locomotor stimula nt effects of cocaine was evident after 1 d, 1 week, and 1 month, but not 2 months of withdrawal. A similar time course was observed for the enhanced efficacy of cocaine-induced inhibition of nucleus accumbens neurons, whether cocaine was administered systemically or locally by m icroiontophoresis. Nucleus accumbens neurons also exhibited sensitized inhibitory responses to iontophoretically applied GABA after 1 d of w ithdrawal, but not later times. These findings suggest that cocaine se nsitization is relatively persistent, but not necessarily permanent, a nd support the hypothesis that expression of behavioral sensitization to cocaine involves actions within the NAc, particularly those mediate d by dopamine D1 receptors.