Functional correlation between subclasses of brain adenosine receptor affinities and ethanol-induced motor incoordination in mice.
To further investigate if the modulation of ethanol-induced motor incoordination is by brain adenosine A1 and/or A2 receptor, adenosine analogs with wide variability in their affinity for A1 and A2 subtypes were administered ICV and their effect on ethanol-induced (IP) motor incoordination was evaluated by rotorod. A dose-dependent marked accentuation of ethanol-induced motor incoordination by adenosine agonists (CHA, NECA, CPA, DCCA) tested, with nearly no effect on normal motor coordination in the absence of ethanol, was observed. There was a positive correlation between A2 affinity, A2/A1 affinity ratio but a negative correlation between A1 affinity and the potency (ED50) of adenosine agonists to accentuate ethanol-induced motor incoordination. However, with the high potency of CHA and NECA, both having significant affinity for A1 and A2 receptors, together with the well known membrane perturbation by ethanol, it seems difficult to rule out until more information becomes available the contribution of A1 receptor activation to adenosine modulation of ethanol-induced motor incoordination. The high density of high affinity A2 (A2a) in the striatum and of A1 in the cerebellum and several brain areas and the known importance of these two brain areas in the motor control, indirectly supports or at least provides a circumstantial evidence for a functional correlation between ethanol-induced motor incoordination and brain adenosine receptors.
Dar
M S
MS
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*
D011983:Receptors, Purinergic; C063165:1-deaza-2-chloro-N(6)-cyclopentyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D000431:Ethanol; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine