Discriminative stimulus properties of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT).

Using a two-lever operant procedure, eleven rats were trained to discriminate 0.2 mg/kg of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT) from saline using a variable-interval 15 sec schedule of reinforcement. Once trained, these animals were used in a series of stimulus generalization and stimulus antagonism studies. The 8-OH DPAT-stimulus did not generalize to the 5-HT1B agonist 1-(3-trifluoromethylphenyl) piperazine (TFMPP) or the 5-HT2 agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), nor could it be attenuated by pre-treatment of the animals with the 5-HT2 antagonist ketanserin. Low doses of spiperone and propranolol were without effect on 8-OH DPAT-appropriate responding, whereas higher doses of these agents resulted in disruption of behavior. Some preliminary structure-activity data were also obtained using several related tetralin analogs. The results of this study demonstrate that the serotonin agonist 8-OH DPAT serves as a discriminative stimulus in rats and that it produces stimulus effects that are probably not 5-HT1B or 5-HT2-mediated.