title: Influence of adenosine receptor agonists on benzodiazepine withdrawal signs in mice.
abstract: The involvement of adenosine receptor agonists in benzodiazepine withdrawal signs was evaluated as the seizure susceptibility of mice. The concomitant administration of subthreshold dose of pentetrazole (55.0 or 60.0 mg/kg, s.c.) with flumazenil (10.0 mg/kg, i.p.) in mice chronically treated with temazepam or diazepam induced the appearance of withdrawal signs: clonic seizures, tonic convulsions and death episodes. The administration of the selective A1 (CPA-N6-cyclopentyladenosine), A2A (CGS 21680-2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride) and the non-selective A1/A2A (NECA-5'-N-ethylcarboxamidoadenosine) adenosine receptor agonists (i.p.) evoked the significant attenuation of benzodiazepine withdrawal signs, and these effects were more expressed in temazepam- than in diazepam-dependent mice. CPA has shown the most apparent and dose-dependent attenuating effect. The results confirm that adenosine A1 and A2A receptors are involved in benzodiazepine withdrawal signs, and adenosine A1 receptor plays a predominant role in this phenomenon.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Staszica 4, 20-081 Lublin, Poland. alistos@op.pl
authors.forename: Joanna
authors.initials: J
authors.lastname: Listos
authors.forename: Danuta
authors.initials: D
authors.lastname: Malec
authors.forename: Sylwia
authors.initials: S
authors.lastname: Fidecka
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects*; D003975:Diazepam / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology; D058913:Purinergic Agonists; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D013693:Temazepam / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D010627:Phenethylamines; D058913:Purinergic Agonists; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D001569:Benzodiazepines; D019830:Adenosine-5'-(N-ethylcarboxamide); D005442:Flumazenil; C048599:N(6)-cyclopentyladenosine; D013693:Temazepam; D000241:Adenosine; D003975:Diazepam; D010433:Pentylenetetrazole