Pineal melatonin in rats: suppression by the selective α2-adrenoceptor agonist medetomidine

This study was done to clarify the role of α2-adrenoceptors in the regulation of pineal melatonin synthesis. A selective α2-adrenoceptor agonist, medetomidine, and antagonist, atipamezole, were injected subcutaneously into rats and their pineal melatonin contents were measured by radioimmunoassay. Medetomidine (120 μg/kg) suppressed melatonin at night to a similar extent during the rising and descending phase of melatonin synthesis, but it did not affect the daytime level. A dose of 12 μg/kg was ineffective; doses of 30–180 μg/kg suppressed nocturnal melatonin levels close to the daytime levels. Significant suppression was reached within 15 min and the effect started to fade 3 h after the injection (120 μg/kg). At midday, medetomidine did not inhibit isoproterenol-stimulated synthesis of melatonin. Atipamezole (0.4 or 1.2 mg/kg) had no effect alone, but it counteracted the medetomidine-induced suppression. The effects of α2-adrenoceptor ligands on melatonin synthesis depend on the time of day and/or on the activity of the pineal sympathetic nerves.