title: Discriminative stimulus effects of melatonin in the rat.
abstract: To provide initial information on the potential mechanisms underlying the discriminative stimulus effects of melatonin, rats were trained to discriminate melatonin (150 mg/kg, IP) from saline in a two-choice discrete-trial avoidance paradigm. Stimulus generalization curves for melatonin were steep; complete generalization with melatonin occurred at 100-150 mg/kg. Triazolam generalized completely with melatonin (n = 7). Flurazepam generalized completely with melatonin in only two out of six rats; however, partial generalization was produced in the remaining four animals. The melatonin-appropriate responding produced by triazolam was antagonized completely (in six out of seven rats) by 0.3-10 mg/kg flumazenil (Ro 15-1788). In contrast, the dose of flumazenil sufficient to block completely the melatonin-like discriminative effects of triazolam failed to block the stimulus effects of the training dose of melatonin. Pentobarbital produced primarily melatonin-appropriate responding, with complete generalization with melatonin in five out of seven rats. Diphenhydramine generalized completely with melatonin in two out of seven rats; however, little or no partial generalization was observed in the remaining five rats. These results suggest that melatonin may produce its discriminative effects through sites on the GABAA-benzodiazepine receptor complex distinct from the benzodiazepine binding sites.
authors.affiliation: Interneuron Pharmaceuticals Inc., Lexington, MA 02173.
authors.forename: T R
authors.initials: TR
authors.lastname: Levesque
authors.forename: K W
authors.initials: KW
authors.lastname: Locke
mesh_terms: D000818:Animals; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D005795:Generalization, Stimulus / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats
chemical_list: D006993:Hypnotics and Sedatives; D005442:Flumazenil; D008550:Melatonin