D-1 and D-2 dopamine receptor blockade: interactive effects in vitro and in vivo

CF Saller and AI Salama

Haloperidol, at low concentrations that block D-2 dopamine (DA) receptors but not D-1 DA receptors (less than 10 microM), potentiated the enhancement of adenylate cyclase activity produced by the D-1 agonist SKF 38393. Low concentrations of haloperidol (less than or equal to 5 microM) also potentiated the K+-evoked release of [3H]acetylcholine from superfused striatal tissue slices. Both of these effects of haloperidol were blocked by nanomolar concentrations of SCH 23390, a D-1 receptor antagonist. In addition, SCH 23390 reduced the ability of haloperidol to antagonize the inhibition of [3H]acetylcholine release produced by the DA agonist apomorphine. By itself, SCH 23390 did not alter either basal adenylate cyclase activity or the K+-evoked release of [3H]acetylcholine. These findings suggest that SCH 23390 can attenuate in vitro responses to D-2 receptor blockade. Likewise, in vivo, very low doses (less than 1 microgram/kg) of SCH 23390 reduced the ability of haloperidol to elevate striatal DA metabolite concentrations and plasma prolactin concentrations. Thus, D- 1 receptor blockade may attenuate the effects of D-2 DA receptor blockade both in vitro and in vivo.

Volume 236, Issue 3, pp. 714-720, 03/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				J. L. Waddington Functional interactions between D-1 and D-2 dopamine receptor systems: their role in the regulation of psychomotor behaviour, putative mechanisms, and clinical relevance J Psychopharmacol, January 1, 1989; 3(2): 54 - 63. [PDF]