Haloperidol- and SCH23390-induced dopaminergic supersensitivities are not additive in the rat.
The effect of chronic D-1 and/or D-2 dopamine receptor blockade on apomorphine-induced behaviors was studied in rats treated for 21 days with the selective D-1 antagonist SCH23390, the predominantly D-2 antagonist haloperidol, and the combination of the two drugs at the same daily doses (0.1 and 1 mg/kg respectively). Apomorphine (0.3 mg/kg) 4 days following the last injection of the drugs increased (49-70%) stereotypic behavior in all animals as compared to saline-treated controls. Although the SCH23390-induced increase was lower than haloperidol-induced supersensitivity, stereotypies after combined administration of both drugs did not differ significantly from either, suggesting that the effects of the two drugs are not additive. Underlying receptor changes and modified D-1/D-2 receptor interactions may account for the participation of both receptor subtypes to the development of neuroleptic-induced dopaminergic supersensitivity.
Parashos
S A
SA
National Institute of Neurological and Communicative Disorders and Stroke, Department of Health and Human Services, US Public Health Service, Bethesda, MD 20892.
Barone
P
P
Marin
C A
CA
Paraschos
A J
AJ
Kapitzoglou-Logothetis
V
V
Chase
T N
TN
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D001552:Benzazepines; D006220:Haloperidol