Effect of melanotropin release inhibiting factor on changes by haloperidol and centbutindole in cerebral cortical 5-hydroxytryptamine receptors.
The effect of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2, MIF) was determined on changes induced by two neuroleptics, haloperidol and centbutindole, in cerebral cortical 5-hydroxytryptamine (5-HT) receptors. Male Sprague-Dawley rats were injected daily i.p. with vehicle, haloperidol (1.0 mg/kg) or centbutindole (0.5 mg/kg), respectively, for 21 days. On day 22, these 3 groups were further divided into 2 subgroups and injected with either vehicle or MIF (2.0 mg/kg, i.p.) daily for 3 days. 3H-5-HT was used to study 5-HT1 receptors, and 3H-spiroperidol to label 5-HT2 receptors in the cerebral cortex. Chronic administration of haloperidol significantly increased (39.7%) the maximal binding capacity (Bmax) of 3H-5-HT binding to 5-HT1 receptors. Dissociation constant (Kd) values did not change. Centbutindole had no effect on 5-HT1 receptors. MIF had no effect on 5-HT1 receptors, nor did it alter haloperidol-induced increases in the Bmax of 3H-5-HT binding to 5-HT1 receptors. Chronic administration of centbutindole significantly increased (61.1%) the Bmax of 3H-spiroperidol binding to 5-HT2 receptors. No change occurred in the Kd values. Chronic treatment with haloperidol had no effect on 5-HT2 receptor characteristics. MIF had no effect on 5-HT2 receptors or on the increase in 5-HT2 receptor density induced by centbutindole. The behavioral syndrome induced by 5-hydroxytryptophan (5-HTP) (50, 100 and 200 mg/kg, i.p.) was also measured in rats treated chronically with haloperidol or centbutindole. Haloperidol had no effect on the 5-HTP syndrome, whereas centbutindole stimulated by 24-45% the intensity of the syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Gulati
A
A
Department of Pharmacodynamics, University of Illinois, Chicago Health Sciences Center.
Bhargava
H N
HN
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D006220:Haloperidol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D011719:Pyrazines; D011985:Receptors, Serotonin; C039923:centbutindole; D009075:MSH Release-Inhibiting Hormone; D006220:Haloperidol