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Mechanism of dexamphetamine‐induced mydriasis in the anaesthetized rat
Author(s) -
Hey J.A.,
Ito T.,
Koss M.C.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11781.x
Subject(s) - mydriasis , yohimbine , idazoxan , phenoxybenzamine , reserpine , endocrinology , medicine , methysergide , chemistry , antagonist , anesthesia , prazosin , propranolol , receptor
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 α 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 α 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 α‐methyl‐ p ‐tyrosine (2 × 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 α 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).