This exploratory/developmental proposal (R21) evaluating potential rewarding aspects of ethanol in the central nervous system and therefore the etiology of alcoholism is relevant to the NIAAA mission. Opioid peptides have been implicated in """"""""rewarding"""""""" behaviors, including food and alcohol ingestion. The theory that opioids impact alcohol imbibition is fairly well accepted, reflected by the use of the opioid receptor antagonist naltrexone as a treatment for alcohol abuse. In addition to the observation that opioid administration affects alcohol intake it has been found that alcohol intake affects the opioidergic system. The concept that eating leads to release of opioids, which then maintain food intake might also be applied to ingestion of alcohol. Alcohol, like palatable foods, is reinforcing. Gatto et al demonstrated that alcohol preferring rats self-administer 100 mg% ethanol into the ventral tegmental area. We hypothesized that central administration of ethanol bypasses the aversive effects of ingesting ethanol, perhaps due to orosensory cues, and instead results in a positive hedonic state. As expected, central administration of ethanol did not condition a taste aversion as has been observed with peripheral administration of alcohol. Rather, central administered ethanol resulted in conditioned taste preference acceptance when paired with saccharin intake. Also, subcutaneous injection of naloxone 15 minutes before central administration of ethanol blocked the ethanol-induced intake of saccharin. Based on the above data our hypothesis is that the reinforcing effects of ethanol are mediated in part by the opioidergic system in brain sites associated with rewarding behaviors.
The specific aims of this project are to establish 1) whether the intake and behavior patterns for ethanol-induced effects are dose dependent; 2) to determine if an opioid antagonist blockade will dose dependently alter the ethanol-induced intake or behavior; 3) to locate specific sites of ethanol action and measure the induced behavior and intake patterns; and 4) to develop a neural map of intake sensitivity to ethanol (cFos-immunohistochemistry, intake/preference studies). Experiments designed to accomplish these aims will provide important information on the relationship between ethanol and opioids along the palatability reward pathways of the central nervous system that lead to ethanol-induced addiction.
