? Marijuana is undoubtedly the most abused illicit drug in the world. The active ingredient in marijuana is delta-9-tetrahydrocannabinol, a member of the cannabinoid family for which there are two known receptors: CB1 (primarily CNS) and CB2 receptors. We will test the hypothesis that intra-VTA CB1 receptor activation with the synthetic agonist CP55, 940 can induce hyperactivity and that these receptors are located on GABA neurons within the VTA. Furthermore, we will test the hypothesis that normal GABA function is necessary for the behavioral effects of intra-VTA CP55, 940 infusion by selectively lesioning the GABA neurons within the VTA followed by subsequent CB1 agonist administration. The observation that acute microinfusion of the cannabinoid agonist CP55, 940 into the reward pathway results in hyperactivity would support the hypothesis that cannabinoids utilize similar circuitry as other abused drugs (e.g., cocaine, amphetamines, heroin, etc.) and suggest that the systemic effects of cannabinoids are a composite of actions in the mesoaccumbens and other pathways. These data are, therefore, critical in elucidating the rewarding/reinforcing effects of cannabinoid agonists. ? ? ? ?
