PMID: 6967676Jan 1, 1980Paper

Effects of chronic treatment with l-sulpiride and haloperidol on central monoaminergic mechanisms

Advances in Biochemical Psychopharmacology
K FuxeR Schwarcz

Abstract

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.

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