Effects of chronic treatment with l-sulpiride and haloperidol on central monoaminergic mechanisms.
Chronic treatment with l-sulpiride (20 mg/kg, twice daily) and haloperidol (0.2 mg/kg, twice daily) for 2 weeks produced behavioral signs of DA receptor supersensitivity in both the striatum and the nucleus accumbens-tuberculum olfactorium region. Thus, 48 hr after treatment apomorphine-induced locomotion, total activity, and rearing activity was significantly enhanced. These behavioral results were correlated with 10% increases in the number of binding sites for the DA agonist 3H-ADTN and the DA antagonist 3H-spiperone in striatum, but the latter sites appeared to be markedly increased in number in the subcortical limbic region. A marked loss of stereoselectivity was demonstrated in the 3H-ADTN binding site, a change that could also in part be involved in producing the signs of enhancement of DA effector mechanisms observed. A corresponding loss of stereoselectivity was not observed in the 3H-spiperone binding site to which, instead, the (+)-butaclamol had an increased affinity. Haloperidol, but not l-sulpiride, in the doses used produced a further enhancement of degeneration-induced supersensitivity at DA receptor sites.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001679:Biogenic Amines / Q000502:physiology*; D001921:Brain / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology; D007051:Ibotenic Acid / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D051381:Rats; D013469:Sulpiride / Q000494:pharmacology*; D013997:Time Factors
D001679:Biogenic Amines; D006892:Hydroxydopamines; D007051:Ibotenic Acid; D013469:Sulpiride; D006916:5-Hydroxytryptophan; D006220:Haloperidol; D001058:Apomorphine