Microdialysis of the Pontine Reticular Formation Revels Inhibition of Acetylcholine Release by Morphine

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Abstract

Background

Systemically administered morphine inhibits rapid eye movement (REM) sleep; however, the neuronal mechanisms through which morphine disrupts REM sleep remain poorly understood. Recently, the authors have shown that morphine-mediated REM sleep inhibition is localized to a specific region of the pontine reticular formation: the gigantocellular tegmental field (FTG). Because cholinergic neurotransmission in the FTG is known to play a role in REM sleep generation, the present study examined the hypothesis that systemically administered morphine would cause decreased acetylcholine release in the FTG.

Methods

Microdialysis probes were stereotaxically positioned in the FTG of six barbiturate-anesthetized cats to measure acetylcholine release. Cholinergic input to the FTG arises from the laterodorsal (LDT) and pedunculopontine tegmental (PPT) brain stem nuclei. By electrically stimulation-evoked acetylcholine release in the FTG. Morphine sulfate (MSO4) was administered intrvenously (500 μg·kg-1). High performance liquid chromatography with electrochemical detection was used to measure stimulation-evoked acetylcholine release in the FTG before and after the systemic administration of morphine sulfate.

Results

Acetylcholine release in the pontine FTG was depressed significantly (P< 0.01) by systemic morphine sulfate. Acetylcholine release without electrical stimulation of the LDT and PPT averaged 0.6 ± 0.18 (mean ± SD) pmol/10 min of dialysis. Before morphine sulfate was administered, electrical stimulation of cholinergic LDT and PPT neurons increased acetylcholine release within the FTG to 1.9 ± 0.76 pmol/10 min. After morphine sulfate was administered, there was a 37% decrease in acetylcholine release within the FTG to average values of 1.2 ± 0.63 pmol/10 min. There was no significant effect of morphine sulfate on spontaneous acetylcholine release in the absence of LDT and PPT stimulation.

Conclusions

Because FTG levels of acetylcholine release increase during REM sleep, the present results are consistent with the hypothesis that diminished acetylcholine release in the pontine FTG comprises one mechanism by which morphine inhibits REM sleep.

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