INFLUENCE OF THE BEHAVIORALLY ACTIVE PEPTIDES ACTH(1-10) AND ACTH(4-10) ON THE MELATONIN MODULATION OF H-3 FLUNITRAZEPAM RECEPTOR-BINDING IN THE RAT CEREBRAL-CORTEX

Possible interactions of ACTH-like peptides with melatonin regulation of central-type benzodiazepine (BNZ) receptors have been studied by me ans of high-affinity H-3-flunitrazepam binding to rat cerebral cortex membrane preparations. Intracerebroventricular injections of melatonin produce a dose-dependent increase in B-max in pinealectomized rats, w ithout changes in KD. Analogous effects were obtained after intracereb roventricular injection of melatonin in adrenalectomized and in adrena lectomized plus pinealectomized rats, which indicated the lack of part icipation of adrenal steroids in this response. Moreover, intracerebro ventricular injection of ACTH(1-10) induced a similar dose-dependent i ncreased B-max in sham-operated animals, whereas pinealectomy, but not adrenalectomy, partially counteracted this effect of ACTH(1-10) admin istration. Besides, simultaneous injection of ACTH(1-10) plus melatoni n reverses the effects of pinealectomy, resulting in an additive effec t of both compounds on B-max. The response obtained when using ACTH(4- 10) was somewhat different, because no dose response was obtained in a ny experiment. Although lack of endogenous melatonin partially reduced the increasing effect of ACTH(4-10) on B-max there were no additive e ffects at the different doses used. The results strongly suggest that ACTH-like peptides, in addition to melatonin, play a role in regulatin g central-type rat BNZ receptors.