The neurobiological substrates of alcohol abuse and alcoholism have been under significant investigation for the last two decades. Research has indicated alcohol can affect the central nervous system through specific neurotransmitter receptors that include glutamate (Glu), gamma-aminobutyric acid (GABA) and Serotonin (5-HT) neuronal systems. Recent investigations of the rates of local cerebral glucose utilization in the brains of rats consuming alcohol suggest specific regions to be activated compared to sucrose consuming controls. These data suggest that different brain regions are involved in alcohol drinking. However, it is not known which neurotransmitter systems in these regions are involved. This grant application proposes to further investigate these neuronal systems by using neurotransmitter turnover rate (TOR) measurements. The turnover rates of aspartate, Glu, GABA, dopamine, norepinephrine and 5-HT will be concurrently determined in small brain regions of rats either prior to (pre-alc group)or following a session of alcohol consumption (post-ale group) and in rats following a session of sucrose (sucrose group) or water (water group consumption. This design will permit assessments of the effects of alcohol consumption in rats with a similar history of alcohol intake (comparing pre-alc group with post-alc group), with vehicle (comparing post-alc group with water group) and the effects of oral consumption of another reinforcer (comparing post-alc group with the sucrose group). A second experiment will assess the TOR of the same neurotransmitters in similar groups of rats, but during the initial phase of alcohol, sucrose and water consumption prior to any major pharmacological actions of alcohol. The data from the second experiment will be compared with the first to determine if a subset of or separate neuronal systems are involved in the initiation of alcohol drinking and what systems are dependent upon the pharmacological actions of alcohol. It is expected that some candidate neuronal systems will be identified in these two neurotransmitter TOR studies that can be further characterized with intracranial injections of specific receptor antagonists, alkylating agents or neurotoxins and microdialysis procedures. The proposed experiments will hopefully add significant new information to our understanding of the processes underlying alcohol abuse.
| Smith, James E; Co, Conchita; McIntosh, Scott et al. (2008) Chronic binge-like moderate ethanol drinking in rats results in widespread decreases in brain serotonin, dopamine, and norepinephrine turnover rates reversed by ethanol intake. J Neurochem 105:2134-55 |
