Diltiazem suppresses quinpirole-induced oral stereotypies in haloperidol withdrawn rats.
1. Tardive dyskinesia (TD) is one of the most serious untoward effects of chronic neuroleptic therapy. Dopaminergic receptor sensitization is assumed to be involved in its pathogenesis. 2. Male Wistar rats were administered (b.i.d.) intragastrically haloperidol (2 mg/kg), diltiazem (5 mg/kg), diltiazem plus haloperidol, and water (controls), for 21 days. 3. Forty eight hours after withdrawal the rats were injected ip with 0.3 mg/kg of quinpirole and observed for stereotypic behaviors (rearing, grooming, licking, and tongue protrusions). 4. There was a significant overall between-group difference in the duration of grooming and the number of tongue protrusions. The haloperidol withdrawn rats scored markedly higher than control and diltiazem alone treated rats. 5. Conjoint treatment with diltiazem and haloperidol prevented the increase of tongue protrusion episodes. 6. We conclude that concurrent diltiazem and haloperidol administration can prevent the occurrence of some behavioral manifestations of dopaminergic receptor supersensitivity, including a lingual dyskinesia.
Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill.
O
O
Pucilowski
B
B
Eichelman
D000704:Analysis of Variance; D000818:Animals; D004110:Diltiazem / Q000494:pharmacology*; D015259:Dopamine Agents / Q000037:antagonists & inhibitors*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy; D004873:Ergolines / Q000037:antagonists & inhibitors*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy
D015259:Dopamine Agents; D004873:Ergolines; D019257:Quinpirole; D004110:Diltiazem; D006220:Haloperidol