title: Adenosine signaling in reserpine-induced depression in rats.
abstract: A single, 6 mg/kg intraperitoneal injection of reserpine increased floating time during forced swim testing 24h after administration in rats in five experiments. Although such behavioral depression traditionally is attributed to drug-induced depletion of brain monoamines, we examined the potential contribution of adenosine signaling, which is plausibly activated by reserpine treatment and contributes to behavioral depression in other paradigms. Whereas peripheral administration of the highly selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.5, 1.0, or 5.0mg/kg i.p.) 15 min before swim testing failed to improve performance in reserpine-treated rats, swim deficits were completely reversed by 7 mg/kg of the nonselective receptor antagonist caffeine. Performance deficits were also reversed by the nonselective A2 antagonist 3,7-dimethylxanthine (0, 0.5, 1.0mg/kg i.p.), and the highly selective A2A receptor antagonist (CSC: 8-(3 chlorostyral)caffeine) (0.01, 0.1, or 1.0mg/kg i.p.) in a dose-dependent manner. The highly selective A2B antagonist alloxazine had no beneficial effect on swim performance at any dose under study (0.1, 1.0, and 5.0mg/kg i.p.).
authors.affiliation: Department of Psychology, University of California, Campus Box 156304, Los Angeles, CA 90095-1563, USA. Electronic address: minor@psych.ucla.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Minor
authors.affiliation: Department of Psychology, University of California, Campus Box 156304, Los Angeles, CA 90095-1563, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Hanff
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D018759:Adrenergic Uptake Inhibitors / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D003866:Depressive Disorder / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005415:Flavins / Q000494:pharmacology; D008297:Male; D009483:Neuropsychological Tests; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012110:Reserpine / Q000633:toxicity*; D013550:Swimming; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D005415:Flavins; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C053907:8-cyclopentyl-1,3-dimethylxanthine; D002110:Caffeine; C008173:isoalloxazine; D012110:Reserpine; D013806:Theophylline; D000241:Adenosine
keywords: A(2A) receptor; Adenosine; Conservation-withdrawal; Major depression; Reserpine