Diazepam attenuates the antagonism of haloperidol against apomorphine-induced stereotypic behavior after subchronic but not acute treatment in rats.
Apomorphine-induced stereotypic behavior was investigated in rats treated with diazepam or haloperidol and with the combination of both drugs in a one day trial or subchronically. The drugs were administered via the drinking water. Diazepam dose-dependently reduced apomorphine stereotypies after the subchronic (6 days) but not after the acute treatment. Haloperidol suppressed apomorphine-induced stereotypic behavior dose-dependently after acute as well as after subchronic administration apparently without the development of tolerance. This discrepancy to other studies may be explained by the concomitant increase in maximum number of D2-receptors in the striatum. The apomorphine antagonistic effect of haloperidol was attenuated when the neuroleptic was administered subchronically in combination with the benzodiazepine. This finding was unexpected since both drugs reduced apomorphine-induced stereotypic behavior when administered alone. The further increase in maximum number of D2-receptors due to combined treatment with low doses of diazepam, suggesting a sort of "over adaptation", possibly explains the haloperidol-antagonistic action of diazepam in the behavioral experiments. Binding studies on dopamine (D1), 5-hydroxytryptamine (5-HT2) and benzodiazepine receptors revealed that modification of the apomorphine-induced stereotypies by the combined treatment with haloperidol and diazepam cannot be explained by interactions of the drugs at the level of the D1, 5-HT2 or benzodiazepine-receptors.
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects*
D004338:Drug Combinations; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D006220:Haloperidol; D001058:Apomorphine; D003975:Diazepam