Autonomic mechanisms for morphine and amphetamine mydriasis in the rat

Morphine sulfate and amphetamine sulfate dilate the pupil of the conscious, unrestrained rat. To examine the mechanisms underlying amphetamine and morphine mydriasis, the pupil diameter of freely moving rats was measured from photographs taken before and after these drugs were administered s.c., i.c.v. or by instillation into the eye. Some rats received monoamine antagonists, sympathetic denervation, or adrenalectomy before drug administration. The results indicate that both amphetamine and morphine mydriasis are primarily due to centrally mediated inhibition of parasympathetic outflow, although for both drugs there may be a sympathetic component. Pharmacological evidence indicates that the mydriatic effect of a low dose of amphetamine is mediated by actions on both alpha-1 and alpha-2 adrenergic receptors, whereas only alpha-2 adrenergic receptors are involved in morphine mydriasis.