title: Effects of melatonin in a place preference conditioning depend on the time of administration.
abstract: 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 days 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.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. nfpapp@cyf-kr.edu.pl
authors.forename: Mariusz
authors.initials: M
authors.lastname: Papp
authors.forename: Ewa
authors.initials: E
authors.lastname: Litwa
authors.forename: Magdalena
authors.initials: M
authors.lastname: Łasoń-Tyburkiewicz
authors.forename: Piotr
authors.initials: P
authors.lastname: Gruca
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D017440:Photoperiod; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; C120267:S 22153; D013876:Thiophenes; D000661:Amphetamine; D008550:Melatonin