Altered activity of midbrain dopamine neurons following 7-day withdrawal from chronic cocaine abuse is normalized by D2 receptor stimulation during the early withdrawal phase.

Using in vivo single-unit recording in rats, we compared the effects of continuous cocaine infusion via minipump or single daily injections (both 40 mg/kg/d x 14 days, S.C.) on the activity of putative dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA). On days 1-5 after cocaine withdrawal, animals were further treated with single daily injections of DA agonists. On withdrawal day 7 continuous cocaine caused a reduction in spontaneously active neurons in the SNC and reduced bursting in the VTA. In contrast, intermittent cocaine resulted in an increase in the number of active neurons in the VTA. These changes were all reversed by apomorphine or quinpirole given during the first 5 withdrawal days. The D1 antagonist SCH 39166 did not antagonize the effects of apomorphine in either region. The role of D2 receptors in modulating baseline DA activity during intermediate cocaine withdrawal is discussed.