Effects of melatonin in a place preference conditioning depend on the time of administration

A conditioned place preference paradigm was used to assess potential rewarding properties of melatonin. the conditioning with melatonin was carried out at two periods of the 12-h light/dark cycle: in the morning (08.30-10.00) and in the evening (18.30-20.00). morning administration of melatonin (2.5,5 and 10 mg/kg) did not support conditioned place preference. in contrast,evening conditioning with melatonin caused a clear shift towards the drug-paired side. this effect was dose-dependent; higher doses of 2.5,5,10 and 50 mg/kg induced conditioned preference while lower doses of 0.5 and 1 mg/kg were ineffective. the increase in the side preference induced by the two most effective doses of melatonin (10 and 50 mg/kg) were comparable to that induced by 1 mg/kg of amphetamine,and was significantly attenuated by the melatonin antagonist,s 22153 (20 mg/kg). in chronic experiment,melatonin (10 mg/kg) caused similar increase of the time spent on conditioned side both in animals administered vehicle for 7 day s and in rats receiving 10 mg/kg of melatonin for the same period of time. potent activity in the conditioned preference model suggests that melatonin may have rewarding properties,which moreover,is not tolerated following repeated pre-exposure to the drug. these findings may indicate potential abuse liability of melatonin,and therefore,its use by humans should require a careful monitoring for abuse and/or dependency. copyright © 2010 by institute of pharmacology polish academy of sciences.