Mechanism of morphine-induced miosis in the dog.
It was observed that dogs under 50 percent nitrous oxide and succinylcholine exhibited a moderately large pupil, maintained a good pupillary light reflex and had a relatively high sensitivity to the miotic effects of morphine.  A cumulative dose of 1 mg/kg. i.v. of morphine caused marked and sustained miosis in these animals.  Morphine, 1 mg, was found to have no pupillary effect by intraocular administration.  Optic nerve section and cervical sympathectomy did not interfere with the miotic response in either acute or chronic preparations.  Conversely, a cumulative i.v. dose of 30 mg/kg of morphine failed to cause pupillary constriction when oculomotor innervation had been interrupted.  In addition, morphine, 0.2 to 0.6 mg/kg i.v., caused marked miosis in dogs whose occipital lobes or cerebral hemispheres had been removed.  These findings suggest that morphine acts on a subcortical region causing constriction of the pupil.  The possible location was ascertained by unit recording with microelectrodes.  It was observed that pupilloconstrictor neurons in the visceral nuclei of the oculomotor nuclear complex responded to morphine, 0.2 mg/kg i.v., by increased frequency of discharge.  Other neurons in the pupillary light reflex pathway showed depressed activity.  Levallorphan, 0.05 mg/kg i.v., but not phenylephrine (locally applied to the conjunctival sac) antagonized all of the actions of morphine on the pupilloconstrictor neurons.  The present findings demonstrate that the miosis induced by morphine is accomplished by an excitatory action of the narcotic on the visceral nuclei of the oculomotor nuclear complex.
D000818:Animals; D000867:Anterior Chamber; D002540:Cerebral Cortex / Q000502:physiology; D002572:Cervical Plexus / Q000502:physiology; D004285:Dogs; D005260:Female; D007267:Injections; D007977:Levallorphan / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009802:Oculomotor Nerve / Q000502:physiology; D009885:Ophthalmology / Q000295:instrumentation; D009900:Optic Nerve / Q000502:physiology; D010775:Photic Stimulation; D011680:Pupil / Q000187:drug effects*; D012025:Reflex, Pupillary / Q000187:drug effects; D013997:Time Factors
D007977:Levallorphan; D009020:Morphine