BEHAVIORAL & PHARMACOLOGICAL ANALYSIS OF DRUGS OF ABUSE

拟议的调查旨在描述和区分

The proposed investigation seeks to characterize and to distinguish a group of serotonergic drugs of abuse in terms of their properties as discriminative stimuli. Emphasis will be upon hallucinogens of the indole/phenethylamine type including lysergic acid diethylamide (LSD] and 2,5-dimethoxy-4-methyl-amphetamine (DOM). In addition, rats will be trained with chlorophenylpiperazine [MCPP], a drug widely used as a probe of serotonergic activity in humans. MCPP-trained subjects will be particularly useful in assessing the functional importance of 5-HT1C receptors. In order to lay a groundwork for the biochemical basis for their stimulus effects, these same drugs will be characterized with respect to their affinities for serotonergic and other selected receptors in the central nervous system and with respect to their ability to alter second messenger systems. Taken together, the use of powerful methods for the assessment of in vivo efficacy (drug discrimination], of in vitro efficacy [stimulation or suppression of second messenger formation], and of affinities for specific receptors (radioligand binding] will provide new understanding of the mode of action of serotonergic drugs, especially those subject to abuse. Thus, biochemical and behavioral experiments will be conducted in parallel. A long-term objective of the proposed research is to achieve an understanding in biochemical terms of these complex behavioral events in animals and thus to facilitate rational treatment interventions for humans.