Modulation of ethanol-induced motor incoordination by mouse striatal A(1) adenosinergic receptor.
We have demonstrated that ethanol-induced motor incoordination is modulated by cerebellar adenosine A(1) receptor. This study represents an extension into another important brain motor area, the striatum that, unlike cerebellum, has high density of both A(1) and A(2A) receptors. Direct intra-striatal micro-infusion of Ro15-4513 (0.05, 0.5, 1 ng), a partial inverse-agonist of benzodiazepine, significantly and nearly dose-dependently attenuated ethanol-induced motor incoordination indicating mediation of ethanol's motor incoordination by striatum. Intra-striatal A(1)-selective agonist N(6)-cyclohexyladenosine (CHA; 1, 2, 4 ng), A(1) = A(2A) non-selective agonist, 5'-N-ethylcarboxamidoadenosine (NECA; 1.5, 3, 6 ng), and A(1)-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 25, 50, 100 ng) dose-dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, strongly suggesting modulation by striatal adenosine A(1) receptor. Intra-striatal DPCPX significantly antagonized not only ethanol-induced motor incoordination but also its potentiation by intra-striatal CHA, R-(+)-N(6)-(2-phenylisopropyladenosine) (R-PIA), or NECA. No change in motor coordination occurred after the highest dose of CHA, R-PIA, or NECA followed by saline. Similarly, the highest intra-striatal dose of Ro15-4513 or DPCPX neither altered motor coordination or locomotor activity indicating relative selectivity of interaction with ethanol. Nearly 25-fold higher dose of A(2A)-selective agonist, CGS-21680, compared to CHA was necessary to produce a comparable potentiation of ethanol's motor incoordination perhaps suggesting a lack of or less significant striatal A(2A) involvement. Intra-striatal pertussis toxin (0.5 microg) pre-treatment markedly attenuated ethanol-induced motor incoordination as well as its potentiation by intra-striatal CHA. These results support that striatum is one of the brain motor areas mediating the motor impairing effects of acute ethanol and that the latter's modulation occurs via A(1)-selective receptors coupled to pertussis toxin-sensitive G proteins.
Dar
M S
MS
Department of Pharmacology, The Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA. darm@mail.ecu.edu
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001259:Ataxia / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D001386:Azides / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D037342:Pertussis Toxin; D010627:Phenethylamines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D000345:Affinity Labels; D000959:Antihypertensive Agents; D001386:Azides; D002492:Central Nervous System Depressants; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D001569:Benzodiazepines; C047235:N-(1-methyl-2-phenylethyl)adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000431:Ethanol; C048599:N(6)-cyclopentyladenosine; C042957:Ro 15-4513; C051360:1,3-dipropyl-8-cyclopentylxanthine; D037342:Pertussis Toxin; D000241:Adenosine