MDMA stimulus generalization to the 5-HT1A serotonin agonist 8-hydroxy-2-(di-n-propylamino)tetralin

The abused substance N-methyl-1-(3,4-methylenedioxyhonyl)-2-aminopropane, o r MDMA, serves as a training drug in animals. Because the 5-HT1A receptor a ntagonist NAN-190 has been shown to partially antagonize the MDMA stimulus. and because NAN-190 binds at several different types of receptors, in the present study we examined other agents (e.g., adrenergic, dopaminergic, sig ma) in tests of stimulus generalization and stimulus antagonism to determin e their influence on the MDMA stimulus. Each of these agents (i.e., clenbut erol, S(-)propranolol, R(+)SCH-23390. amantadine, NANM) was without effect on MDMA-appropriate responding. The binding that NAN-190 behaves as a 5-HT1 A partial agonist in some studies prompted examination of the: 5-HT1A recep tor agonist 8-OH DPAT and its optical isomers. MDMA-stimulus generalization occurred to racemic 8-OH DPAT (ED50 = 9.3 mg/kg), R( +)8-OH DPAT (ED50 = 0 .2 mg/kg), and to the 5-HT1A receptor partial agonist S(-)8-OH DPAT (ED50 = 0.4 mg/kg). The results suggest that the MDMA stimulus might possess a 5-H T1A component of action. Furthermore, because 8-OH DPAT is known to enhance the stimulus effects of hallucinogens as discriminative stimuli, and becau se MDMA reportedly enhances the effects of hallucinogenic agents in humans ("flipping," "candy flipping"), this latter MDMA-induced phenomenon might i nvolve a 5-HT1A mechanism. (C) 2000 Elsevier Science Inc.