Characterization of the discriminative stimulus properties of centrally administered (-)-DOM and LSD

Despite the plausible assumption that the effects of hallucinogens predominantly arise in the central nervous system, most studies of these drugs in intact subjects have been conducted following systemic administration. The objective of the present investigation was to characterize the stimulus effects of (-)2,5-dimethoxy-4-methylamphetamine ((-)-DOM) following intracerebroventricular administration. Chronic indwelling cannulae were implanted into the lateral ventricle of male Fischer 344 rats trained to discriminate systemically administered (-)-DOM or lysergic acid diethylamide (LSD) from saline. Time-course and dose-response relationships for (-)-DOM and LSD administered intracerebroventricularly were established. For both LSD and (-)-DOM, central administration did not change the pretreatment times required for the maximal stimulus effects to occur. However, the onset of the stimulus effect was more rapid following intracerebroventricular administration. Following pretreatment periods that maximize drug-appropriate responding, central administration of (-)-DOM and LSD was approximately 2.4- and 1.5-times more potent, respectively, than systemic administration. The results of this study are consistent with the assumption that the stimulus effects of (-)-DOM and LSD are centrally mediated.