The objectives of the present proposal are to combine and integrate behavioral and biochemical techniques (i) to characterize further the serotonergic-glutamatergic interaction in drug-induced stimulus control by indoleamine and phenethylamine hallucinogens and (ii) to determine the molecular mechanisms involved in this interaction. Thus, behavioral results using drug discrimination, which is widely believed to have significant subjective correlates in humans, will be correlated and compared with various biochemical measures of efficacy such as the in vivo release of neurotransmitter and reversible molecular modifications of the NMDA receptor. This study will utilize techniques of microinjection and microdialysis to create and study conditions at the cellular level present during administration of hallucinogen. The study will also utilize drug discrimination as a way to correlate said conditions with behavior in rats. Hallucinogens are a significant health care problem in adolescents and young adults, with the use of these drugs surpassing that of cocaine. Furthermore, the ability of some hallucinogens to mimic human psychosis suggests that an elucidation of the mechanisms of action of hallucinogenic drugs may contribute to an understanding of schizophrenia and other psychotic disorders.
