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Morphine-induced pupillary fluctuation: physiological evidence against selective action on the Edinger-Westphal
T J Lynch1, P J Tiseo, M W Adler
1Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA.
Abstract:
In the rat, the predominant pupillary effect of morphine sulfate (30 mg/kg, i.p.) is mydriasis, interrupted periodically by miotic excursions. Using infrared video pupillometry, respirometry and EEG recording, we had previously reported that miotic excursions are always correlated with the onset of EEG bursting, while mydriatic excursions are preceded by respiratory slowing and correlated with EEG burst cessation. In the current study, we found that during morphine-induced EEG bursting and related miosis, delivery of an alerting stimulus to the rat caused an immediate conversion sequence composed of respiratory slowing, burst cessation and mydriatic excursion. We also simulated morphine-induced EEG bursting through non-opioid means by delivering kindling electrical stimuli to the amygdala. When the stimulus was given during morphine-induced mydriasis, the stimulus-induced bursting resulted in a miotic excursion identical to spontaneous morphine-induced miotic excursions. These results indicate 1) that the reticular activating system is involved in morphine-induced mydriatic excursions and 2) that EEG bursting is not simply correlated with morphine-induced miotic excursions, but causes them. Collectively, these results strengthen our hypothesis that the Edinger-Westphal nucleus is not the site in which the selective, receptor-mediated pupillary effects of morphine are initiated.
Insights
Morphine causes pupil changes in rats. Alerting stimuli during morphine-induced pupil constriction trigger pupil dilation by affecting brain activity, suggesting the reticular activating system
Area of Science:
- Neuroscience
- Pharmacology
- Ophthalmology
Background:
- Morphine sulfate in rats primarily causes mydriasis (pupil dilation) with intermittent miosis (pupil constriction).
- Previous research linked morphine-induced miosis to electroencephalogram (EEG) bursting and mydriasis to respiratory slowing and EEG burst cessation.
Purpose of the Study:
- To investigate the neural mechanisms underlying morphine-induced pupillary changes in rats.
- To determine the role of the reticular activating system (RAS) and EEG bursting in morphine's pupillary effects.
Main Methods:
- Infrared video pupillometry, respirometry, and EEG recording were employed.
- Alerting stimuli were administered during morphine-induced EEG bursting and miosis.
- Morphine-induced EEG bursting was simulated using electrical amygdala kindling stimuli.
Main Results:
- Alerting stimuli during morphine-induced miosis rapidly induced respiratory slowing, EEG burst cessation, and mydriasis.
- Stimulus-induced EEG bursting, even without morphine, caused miotic excursions similar to spontaneous ones.
- These findings implicate the RAS in morphine-induced mydriasis and establish EEG bursting as a cause, not just a correlate, of miosis.
Conclusions:
- The reticular activating system plays a role in morphine-induced pupillary mydriasis.
- EEG bursting is a causal factor in morphine-induced pupillary miosis.
- These results challenge the Edinger-Westphal nucleus as the primary site for morphine's selective pupillary effects.