Mechanism of dexamphetamine‐induced mydriasis in the anaesthetized rat

Abstract

The effect of intravenous administration of dexamphetamine ((+)‐Amp) on rat pupil diameter was investigated. In all experiments, the vagosympathetic trunks were sectioned bilaterally at the cervical level. In rats anaesthetized with urethane, (+)‐Amp (0.1–0.3 mg kg−1, i.v.) produced a dose‐related increase in pupil size. The mydriatic effects of (+)‐Amp were evident immediately after administration. Pretreatment with the α2‐adrenoceptor antagonists yohimbine (1.5 mg kg−1 i.v.) or idazoxan (0.5 mg kg−1 i.v.) blocked the pupillary response to (+)‐Amp. Yohimbine caused about a 30 fold shift to the right in the dose‐response curve whereas idazoxan almost completely abolished the mydriatic response to (+)‐Amp. In contrast, pretreatment with the α1‐adrenoceptor antagonist phenoxybenzamine (2 mg kg−1, i.v.), failed to alter significantly the pupillary response to (+)‐Amp. Depletion of central nervous system (CNS) monoamines with reserpine (5 mg kg−1 i.p.) and α‐methyl‐p‐tyrosine (2 × 300 mg kg−1, i.p.) prevented the pupillary response to (+)‐Amp. The mydriatic effect of (+)‐Amp was present only in preparations that had intact parasympathetic neural tone to the iris. Central preganglionic denervation of the oculomotor nerve abolished the mydriatic response of (+)‐Amp. These results indicate the (+)‐Amp acts in the CNS to produce mydriasis in the anaesthetized rat by stimulating CNS postsynaptic α2‐adrenoceptors, findings that are consistent with the hypothesis that (+)‐Amp acts predominantly as an indirect sympathomimetic agent to release endogenous stores of a monoaminergic neurotransmitter (perhaps noradrenaline). 1989 British Pharmacological Society