The proposed work is the continuation and extension of initial studies from PI's laboratory which suggested an involvement of adenosine in ethanol-induced motor incoordination in mice. The principle objective of the proposed research, therefore, is to test the hypothesis that adenosine plays an important modulatory role in ethanol-induced motor disturbances. The proposed studies are designed to ascertain the consequences of acute ethanol treatment on ethanol-induced motor incoordination and inhibition of spontaneous motor activity using CD-1 male mouse as the model. Any functional relationship between these behavioral changes and the characteristics of adenosine receptors. the levels of cyclic AMP, the steady state levels of adenosine and its major matabolites inosine and hypoxanthine will be examined in four brain areas: cerebellum, brainstem, striatum and cortex, which are known to modulate normal motor activity.
The specific aims of the proposal are; (1) to test the hypothesis that ethanol-induced motor disturbance are accentuated and attenuated by adenosine agonists and antagonists respectively and that these interactions occur centrally: (2) to investigate the possibility that ethanol-induced motor disturbances involve an alteration in central adenosine and/or its major metabolites level: and (3) to investigate the cellular/subcellular mechanisms involved in the behavioral interactions between ethanol and adenosine.
For specific aims 2 and 3, studies will be conducted in each of the four specified brain areas. The proposed research represents a logical extension of the preliminary reports of adenosine involvement in some CNS effects of ethanol from PI's laboratory which have been, in part, confirmed and extended by others. New information from the proposed studies should provide more insight into the mechanism(s) by which adenosine modulates ethanol-mechanism of ethanol-induced motor disturbances may help in the development of appropriate drug treatment for better clinical management of ethanol-induced ataxia and SMA inhibition and possibly avoid tragic accidents which are primarily due to these adverse effects of alcohol drinking.
| Dar, M S (1992) Selective antagonism of acute ethanol-induced motor disturbances by centrally administered Ro 15-4513 in mice. Pharmacol Biochem Behav 42:473-9 |
| Dar, M S; Clark, M (1992) Tolerance to adenosine's accentuation of ethanol-induced motor incoordination in ethanol-tolerant mice. Alcohol Clin Exp Res 16:1138-46 |
| Dar, M S (1990) Functional correlation between subclasses of brain adenosine receptor affinities and ethanol-induced motor incoordination in mice. Pharmacol Biochem Behav 37:747-53 |
| Dar, M S (1990) Central adenosinergic system involvement in ethanol-induced motor incoordination in mice. J Pharmacol Exp Ther 255:1202-9 |
