Rat striatal adenosinergic modulation of ethanol-induced motor impairment: possible role of striatal cyclic AMP
Section snippets
Animals
Male Sprague–Dawley rats (Charles River, Raleigh, NC, U.S.A.), weighing 150–200 g, were used in the entire study. Following their arrival, the rats were housed individually in polyethylene cages with free access to food and water in a temperature- (24±1°C) and humidity-controlled room. The animals were exposed to a 12-h light/12-h dark day–night cycle, with lights on at 7.00 a.m. All efforts were made to minimize animal suffering, to reduce the number of animals used and to utilize alternatives
Results
As reported previously,28, 291.5 g/kg was the test dose of ethanol used throughout the present investigation. The selection of the test dose was based on a separate dose–response study (data not shown). The test dose of ethanol produced significant motor incoordination with little or no observable sedation. The onset of motor incoordination was rapid and usually reached the maximal level within 15–20 min post-ethanol, followed by the gradual recovery of up to 90% of the normal motor coordination
Discussion
In the present investigation, the intrastriatal microinfusion of the adenosine receptor agonist, CHA, significantly accentuated the motor incoordinating effect of ethanol. The adenosine agonist, however, did not alter the normal motor coordination in the absence of ethanol. This effect of adenosine agonist on EIMI was achieved mainly through the activation of striatal adenosine A1 receptors and was antagonized by the A1 antagonist, DPCPX, as already explained in the Introduction.14, 17, 28, 29
Conclusions
In summary, the results from the present study suggest the involvement of striatal cAMP in the actions of ethanol and its modulation by striatal adenosine. The results of the present and previous investigations28, 29support a significant functional interaction between the striatal adenosinergic system and ethanol. Striatal adenosine and/or adenosine A1 receptors might modulate EIMI through (a) cAMP–PKA-mediated mechanism(s).
Acknowledgements
The authors are grateful to Ms Pam Wynne for her excellent word processing in the preparation of this manuscript.
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Present address: Upjohn Pharmaceutical Company, CNS Research Unit 7251-209-506, Kalamazoo, MI 49001, U.S.A.