Clonidine produces mydriasis in conscious mice by activating central α2-adrenoceptors

Abstract

Intraperitoneal (i.p.) injection of the α 2-adrenoceptor agonist clonidine (1–3000 μg/kg) produed dose-dependent pupil dilatation in conscious C57/B1/6 mice with an ED 50 of 54 μg/kg (95% confidence limits 40–74 μg/kg). This response was rapid in onset and of approximately 30 min duration. The α 2-adrenoceptor antagonists idazoxan (1 or 3 mg/kg i.p.) and yohimbine (1 or 3 mg/kg i.p.) both produced dose-related miosis, but the α 1- and β-adrenoceptor antagonists prazosin (1 or 3 mg/kg i.p.) and pindolol (1 or 3 mg/kg i.p.) were without effect. These doses of idazoxan and yohimbine potently reversed the mydriasis induced by clonidine (100 μg/kg i.p.), while prazosin and pindolol were again ineffective. Clonidine-induced mydriasis was also unaltered by the 5-HT antagonists, methysergide (2.5 mg/kg i.p.) and ketanserin (0.1 mg/kg i.p.) or 0.1 mg/kg i.p. of the dopamine antagonists, haloperidol, SCH 23390 and BRL 34778. A dose of 0.25 μg clonidine, which was ineffective when administered i.p., produced marked mydriasis after intracerebroventricular (i.c.v.) injection. In addition, the mydriasis produced by i.p. injection of clonidine (100 μg/kg) was abolished by i.c.v. dosing of 2.5 μg idazoxan or yohimbine, but again not by prazosin or pindolol. Together, these data provide strong evidence to indicate that clonidine-induced mydriasis is exclusively mediated via central α 2-adrenoceptors and that this response provides a useful model for studying the function of these receptors.