DISCRIMINATIVE STIMULUS EFFECTS OF MELATONIN IN THE RAT

To provide initial information on the potential mechanisms underlying the discriminative stimulus effects of melatonin, rats were trained to discriminate me latonin (150 mg/kg, IP) from saline in a two-choice d iscrete-trial avoidance paradigm. Stimulus generalization curves for m elatonin were steep; complete generalization with melatonin occurred a t 100-150 mg/kg. Triazolam generalized completely with melatonin (n = 7). Flurazepam generalized completely with melatonin in only two out o f six rats; however, partial generalization was produced in the remain ing four animals. The melatonin-appropriate responding produced by tri azolam 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 su fficient to block completely the melatonin-like discriminative effects of triazolam failed to block the stimulus effects of the training dos e of melatonin. Pentobarbital produced primarily melatonin-appropriate responding, with complete generalization with melatonin in five out o f seven rats. Diphenhydramine generalized completely with melatonin in two out of seven rats; however, little or no partial generalization w as observed in the remaining five rats. These results suggest that mel atonin may produce its discriminative effects through sites on the GAB A(A)-benzodiazepine receptor complex distinct from the benzodiazepine binding sites.