DIFFERENTIAL-EFFECTS OF SCH-23390 ON THE APOMORPHINE SUBSENSITIVITY IN THE SUBSTANTIA-NIGRA AND VENTRAL TEGMENTAL AREA 1 DAY FOLLOWING WITHDRAWAL FROM CONTINUOUS OR INTERMITTENT COCAINE PRETREATMENT

Using extracellular single-unit recordings in rats, the effects of chr onic intermittent injections and continuous infusion of cocaine on sin gle dopamine neurons were directly compared in the substantia nigra an d ventral tegmental area. After 1-day withdrawal we determined: (1) th e neuronal sensitivity to the mixed D-1/D-2 agonist apomorphine and (2 ) its modulation by the D-1 antagonist SCH 23390. The nigral dopamine neurons exhibited subsensitivity to the impulse-inhibiting effects of apomorphine following both intermittent and continuous regimens. SCH 2 3390 selectively reversed the apomorphine subsensitivity in the interm ittent group, while having minimal effects in the other group. Dopamin e neurons in the ventral tegmental area, on the other hand, were sub- and normosensitive to apomorphine following intermittent and continuou s dosing regimens, respectively. In contrast to the substantia nigra, SCH 23390 failed to alter the apomorphine sensitivity in either of the pretreatment groups. Possible mechanisms underlying these distinctive changes in the substantia nigra and ventral tegmental area following intermittent and continuous cocaine pretreatment regimens are discusse d.