in vivo characterization of D2/D3 agonists & antagonists

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DESCRIPTION (provided by applicant): The dopamine D2 and D3 receptors are differentially expressed at high levels within the mesolimbic dopaminergic system and the nucleus accumbens, areas known to be important in the regulation of the reinforcing properties of drugs of abuse. It is hypothesized that the dopamine D2 and D3 receptors are differentially involved in reward and reinforcement, and that utilization of selective D2 and D3 agonists and antagonists will allow for a more accurate assessment of the in vivo roles of the D2 and D3 receptors. Assignment of roles for D2 and D3 has been complicated by the fact that there are currently no purely D2 or D3 selective agonists or antagonists, rather existing compounds have varying degrees of selectivity for D2 and D3. The specific aims to be tested are: (1) in vivo characterization of existing and novel dopaminergic agonist and antagonist with regard to their selectivity for, and activities at the D2 and D3 receptors in rhesus monkeys and rats, (2) investigation of the reinforcing properties of D2 and D3 acting agonists and antagonists, and (3) evaluation of D2 and D3 agonists and antagonists with regard to their ability to modulate reinforcement maintained by psychostimulants such as cocaine. Taken together, the results of these experiments will allow for a better understanding of the specific roles of the D2 and D3 receptors in the reward and reinforcement pathways of the brain as well as provide valuable information towards the development of novel compounds as well as therapeutics aimed at drug abuse and addiction.