![]() ![]() As such, DA neurotransmission in the NAc provides the framework for theories exploring the chemoarchitectural substrates of reward and motivation, including aspects of drug addiction. The NAc occupies a prominent position in the ventral striatum and is a main target of the mesotelencephalic DA system. The major focus of most of these investigations has been the mesocorticolimbic dopamine (DA) system originating from the ventral tegmental area (VTA) and projecting towards a wide range of limbic and telencephalic structures including the olfactory tubercle, the amygdala, frontal and limbic cortices, especially the medial prefrontal cortex (mPFC), and the nucleus accumbens (NAc). ![]() In contrast, the neural systems approach has explored the possible commonalities of the effects of such drugs. Consequently, molecular and cellular approaches have emphasized differences in the primary sites of action of drugs of abuse. In order to assess the neuroadaptations occurring within the brain reward systems in response to acute and repeated exposure to drugs of abuse, one must first understand the neurobiological bases of drug reward. One of the main challenges in drug dependence research is to understand the psychobiological dysregulation, and by extension, the molecular, cellular, and system processes that underlie these various phases. ![]() The behavioral progression typically ends with excessive drug intake, loss of control over intake, and vulnerability to relapse. Introduction: drug addiction, the mesolimbic DA system, and the DA D 3 receptorÄrug addiction is a dynamic phenomenon characterized by several key stages: (1) initiation or acquisition of drug-taking, (2) compulsive drug taking, and (3) drug taking coupled with a marked narrowing of the behavioral repertoire. Provided these results can be extrapolated to human drug addicts, they suggest that selective DA D 3 receptor antagonists may prove effective as potential pharmacotherapeutic agents to manage drug dependence and addiction.Ä¡. The results obtained with highly selective D 3 receptor antagonists such as SB-277011-A, SB-414796, and NGB-2904 indicate that central D 3 receptors may play an important role in drug-induced reward, drug-taking, and cue-, drug-, and stress-induced reinstatement of drug-seeking behavior. The purpose of the present article is to review, for the first time, the effects of various putative D 3 receptor selective compounds in animal models of drug dependence and addiction. Currently, with the synthesis and characterization of new highly selective D 3 receptor antagonists such as SB-277011-A this difficulty has been surmounted. The interpretation of results from studies using mixed D 2/D 3 agonists and/or antagonists is problematic because these agents have low selectivity for D 3 over D 2 receptors and it is likely that their actions are primarily related to D 2 receptor antagonism and possibly interaction with other neurotransmitter receptors. However, this hypothesis has been difficult to test due to the lack of compounds with high selectivity for central D 3 receptors. This finding led to the postulate that D 3 receptors may be involved in drug dependence and addiction. Subsequent studies have indicated that D 3 receptors, as well as D 3 receptor mRNA, are primarily localized in limbic regions in mammals. The cDNA for the dopamine D 3 receptor was isolated and characterized in 1990. ![]()
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