Alcohol drinking is influenced by sensitivity to the rewarding effects of alcohol, with increased sensitivity to the low-dose stimulating effects of ethanol (EtOH) being associated with high alcohol preference. Understanding neuronal mechanisms underlying the reinforcing effects of EtOH will greatly advance our knowledge of CMS neurobiological factors that promote high alcohol drinking behavior. The goals of this project are to better understand how neuronal circuits within the meso-cortico-limbic dopamine (DA) system are involved in regulating the reinforcing effects of EtOH. The ventral tegmental area (VTA) dopamine (DA) system has a critical role in the brain reward system, and in mediating the actions of most drugs of abuse, including alcohol. The overall hypothesis to be tested is that """"""""neuronal circuits within the meso-cortico-limbic DA system mediate the response-contingent behavior for the self-infusion of EtOH into the posterior VTA."""""""" This hypothesis will be tested using site selective microinjection, intra-cranial self-administration (ICSA), and in vivo microdialysis techniques. Male Wistar rats will be used in this project. ICSA findings indicate that the posterior VTA is a neuro-anatomical site supporting the reinforcing actions of EtOH, and that activation of DA neurons may underlie these reinforcing effects.
The first aim will extend current studies to examine the involvement of serotonin-2 (5-HT-2) and nicotinic (NIC) receptors in mediating EtOH self-infusion into the posterior VTA.
The second aim will use the combination of ICSA and microdialysis to determine the effects of infusions of EtOH into the posterior VTA on the release of DA in four VTA target sites (i.e., nucleus accumbens shell, central nucleus of the amygdala, medial prefrontal cortex and ventral pallidum).
The third aim will use microinjections of DA antagonists into VTA target sites in combination with ICSA of EtOH to determine the involvement of DA receptors in mediating the response-contingent behavior for the self- infusion of EtOH into the posterior VTA. Overall, the results of this project will provide important information on neuronal mechanisms underlying the rewarding actions of alcohol, which could greatly aid the development of pharmaco-therapies for the treatment of alcoholism and alcohol abuse.
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