Evidence for central alpha(2)-adrenergic modulation of rat pineal melatonin synthesis.

This study was performed to distinguish central and peripheral alpha(2)-adrenoceptors in the inhibition of rat pineal melatonin synthesis. The rats received lipo- or hydrophilic alpha(2)-adrenoceptor ligand injections at middark; after 1 or 2 h the pineal melatonin contents were measured. The lipophilic agonist medetomidine (100 microg/kg s.c.) suppressed the melatonin contents significantly, while the hydrophilic agonists ST-91 and p-aminoclonidine (10 or 100 microg/kg i.v.) did not. The suppression by medetomidine was counteracted by the lipophilic antagonist yohimbine (0.3-3.0 mg/kg i.p.) but not by the hydrophilic antagonist L-659,066 (1-10 mg/kg i.v.). In conclusion, the suppression of nocturnal melatonin synthesis by alpha(2)-adrenoceptor agonists is mainly of central origin.