Studies on the mechanism of clonidine-induced mydriasis in the rat.
Intravenous administration of clonidine hydrochloride (3-100 micrograms/kg) produced a dose-dependent pupillary dilation in anaesthetized rats. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level. Clonidine-induced mydriasis was present only in those preparations having intact parasympathetic neural tone to the iris. Depletion of CNS monoamines by more than 95% with reserpine (5 mg/kg) and alpha-methyl-para-tyrosine (2 X 300 mg/kg) failed to alter the dose-response relation to clonidine. Pretreatment with the alpha-2-adrenoceptor antagonist, yohimbine hydrochloride (1.5 mg/kg), produced about a 10-fold shift to the right in the pupillary dose-response curve to clonidine. Yohimbine administered after the highest dose of clonidine also antagonized the mydriatic response. The above results suggest that clonidine acts on CNS post-synaptic alpha-2-adrenoceptors to produce mydriasis by withdrawal of parasympathetic neural tone to the iris. In an attempt to assess the physiological substrate(s) involved, mydriatic responses, due to parasympatho-inhibition, were evoked by electrical stimulation of ascending (sciatic nerve and medullary) and descending (hypothalamic) pathways. Yohimbine (0.3 and 1.0 mg/kg) produced a dose-dependent inhibition of the pupillary dilation evoked by stimulation of the sciatic nerve and medullary loci, whereas these doses of yohimbine failed to alter the dilation in response to hypothalamic stimulation. Similarly, monoamine depletion greatly antagonized the pupillary dilation elicited by sciatic nerve and medullary stimulation without significantly affecting mydriasis due to hypothalamic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hey
J A
JA
Gherezghiher
T
T
Koss
M C
MC
D000818:Animals; D001921:Brain / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D007498:Iris / Q000294:innervation; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011680:Pupil / Q000187:drug effects*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012018:Reflex; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine