Adenosinergic modulation of ethanol-induced motor incoordination in the rat motor cortex

1. On going work in our laboratory has shown that adenosine modulates ethanol-induced motor incoordination (EIMI) when given systemically as well as directly into the cerebral ventricles, cerebellum and corpus striatum of the rat and/or mouse, 2. The objective of this study was to determine what effect adenosine agonists and antagonists would have within the rat motor cortex on EIMI. 3. The participation of the motor cortex in EIMI was suggested when microinfusion of the anti-ethanol compound, Ro15-4513, an inverse agonist of the benzodiazepine binding site, directly into the motor cortex significantly attenuated EIMI. Further, the adenosine agonists N-6-cyclohexyladenosine (CHA) and 2-p-(2-carboxyethyl)-phenethylamino-5'-N-carboxaminoadenosine hydrochloride (CGS-21680) significantly accentuated EIMI in a dose-related manner. The adenosine A(1) receptor-selective agonist, CHA, appeared most potent in this modulatory effect when compared to the A(2)-selective agonist, CGS-21680. 4. The extent of diffusion of the adenosine drugs within the cortical tissue after their microinfusion was also checked by measuring the dispersion of microinfused [H-3]CHA. The [H-3]CHA dispersion study indirectly confirmed that the results of the present investigation were based on the effect of adenosine drugs within the motor cortex only. 5. Accentuation by the A(1)- and A(2)-selective adenosine agonists was significantly attenuated by the A(1)-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) but not by the A(2) receptor-selective antagonist 8-(3-chlorostyryl)caffeine (CSC) further suggesting modulation mainly by the A(1)-subtype. 6. Pretreatment of the motor cortex with pertussis toxin (TT) significantly reduced the capacity of both A(1)- and A(2)-selective adenosine agonists to accentuate EIMI suggesting the involvement of a PT-sensitive G(i)/G(o) protein. 7. These data support earlier work which showed that adenosine modulates EIMI within the central nervous system (CNS), most likely via the Al receptor, and moreover, extend that work by including the motor cortex as a brain area participating in the adenosinergic modulation of ethanol-induced motor impairment.