D-1 and D-2 dopamine receptor blockade: interactive effects in vitro and in vivo.
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.
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D011388:Prolactin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006220:Haloperidol; D000109:Acetylcholine; D011188:Potassium; D004298:Dopamine