Mechanism of dexamphetamine-induced mydriasis in the anaesthetized rat.

Abstract:

:1. 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. 2. 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. 3. Pretreatment with the alpha 2-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. 4. In contrast, pretreatment with the alpha 1-adrenoceptor antagonist phenoxybenzamine (2 mg kg-1, i.v.), failed to alter significantly the pupillary response to (+)-Amp. 5. Depletion of central nervous system (CNS) monoamines with reserpine (5 mg kg-1, i.p.) and alpha-methyl-p-tyrosine (2 x 300 mg kg-1, i.p.) prevented the pupillary response to (+)-Amp. 6. 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. 7. These results indicate the (+)-Amp acts in the CNS to produce mydriasis in the anaesthetized rat by stimulating CNS postsynaptic alpha 2-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).

journal_name

Br J Pharmacol

authors

Hey JA,Ito T,Koss MC

doi

10.1111/j.1476-5381.1989.tb11781.x

subject

Has Abstract

pub_date

1989-01-01 00:00:00

pages

39-44

issue

1

eissn

0007-1188

issn

1476-5381

journal_volume

96

pub_type

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