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 chronic intermittent injections and continuous infusion of cocaine on single dopamine neurons were directly compared in the substantia nigra and ventral tegmental area. After 1-day withdrawal we determined: (1) the neuronal sensitivity to the mixed D1/D2 agonist apomorphine and (2) its modulation by the D1 antagonist SCH 23390. The nigral dopamine neurons exhibited subsensitivity to the impulse-inhibiting effects of apomorphine following both intermittent and continuous regimens. SCH 23390 selectively reversed the apomorphine subsensitivity in the intermittent group, while having minimal effects in the other group. Dopamine neurons in the ventral tegmental area, on the other hand, were sub- and normosensitive to apomorphine following intermittent and continuous 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 discussed.
Lee
T H
TH
Department of Psychiatry, DUMC 3870, Duke University Medical Center, Durham, NC 27710, USA. leedopam@acpub.duke.edu
Gao
W Y
WY
Ellinwood
E H
EH
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013378:Substantia Nigra / Q000187:drug effects*; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D001552:Benzazepines; D003042:Cocaine; D001058:Apomorphine