title: Chronic ethanol intoxication enhances [3H]CCPA binding and does not reduce A1 adenosine receptor function in rat cerebellum.
abstract: The effects of acute and chronic treatment with ethanol on the function of A1 adenosine receptor in the rat cerebellar cortex were investigated. Acute administration of ethanol (0.5-5 g/kg) had no effect on the binding of the A1-receptor agonist [3H]2-chloro-N6-cyclopentyladenosine ([3H]CCPA) or that the antagonist [3H]8-cyclopentyl-1-3-dipropylxanthine ([3H]DPCPX) in rat cerebellar cortical membranes. Rats were rendered ethanol dependent by repeated forced oral administration of ethanol (12-18 g/kg per day) for 6 days. [3H]CCPA binding was increased by 23% in cerebellar cortical membranes prepared from rats killed 3 h after ethanol withdrawal compared with saline-treated animals. The increase in [3H]CCPA binding was still apparent 12-24 h after the last ethanol administration, but was no longer detectable 3-6 days after ethanol withdrawal. In contrast, the binding of [3H]DPCPX was not modified in the cerebellar cortex of rats killed at various times after ethanol withdrawal. The acute administration of CCPA [0.25-1 mg/kg, intraperitoneally (IP)] suppressed the tremors and audiogenic seizures apparent 24 h after ethanol withdrawal. Moreover, repeated coadministration of CCPA (0.5 mg/kg, IP, four times daily) and ethanol did not prevent the generation of audiogenic seizures during withdrawal but completely prevented mortality. Finally, CCPA antagonized with similar potencies and efficacies the isoniazid-induced convulsions observed in control and ethanol-withdrawn rats. These results indicate that long-term treatment with intoxicating doses of ethanol enhances [3H]CCPA binding but does not reduce the anticonvulsant efficacy of CCPA or the function of A1 adenosine receptors.
authors.affiliation: Department of Experimental Biology, University of Cagliari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Concas
authors.forename: M P
authors.initials: MP
authors.lastname: Mascia
authors.forename: T
authors.initials: T
authors.lastname: Cuccheddu
authors.forename: S
authors.initials: S
authors.lastname: Floris
authors.forename: M C
authors.initials: MC
authors.lastname: Mostallino
authors.forename: C
authors.initials: C
authors.lastname: Perra
authors.forename: S
authors.initials: S
authors.lastname: Satta
authors.forename: G
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000437:Alcoholism / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D007538:Isoniazid; D008297:Male; D008566:Membranes / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D014202:Tremor / Q000139:chemically induced; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C058394:2-chloro-N(6)cyclopentyladenosine; D000431:Ethanol; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D007538:Isoniazid