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Afferent effects on locus coeruleus in opiate withdrawal
1Central Nervous System Research, Eli Lilly and Co., Indianapolis, IN.
Progress in Brain Research
|January 1, 1991
Summary
Opiate withdrawal involves increased locus coeruleus (LC) neuron activity, driven by external brain pathways, not intrinsic changes. Non-NMDA pathways are key, with potential therapeutic benefits from specific NMDA antagonists.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- The locus coeruleus (LC) is implicated in opiate withdrawal.
- LC neuron activity increases during withdrawal, correlating with behavior.
- In vitro studies show afferent pathways to LC are crucial for this activation.
Purpose of the Study:
- To review data on the mechanisms of LC activation during morphine withdrawal.
- To explore the role of excitatory amino acid pathways and intracellular signaling.
- To evaluate the therapeutic potential of NMDA antagonists in opiate withdrawal.
Main Methods:
- Review of existing research data on LC neuron activity during withdrawal.
- Analysis of neurochemical pathways involved in LC activation.
- Assessment of the effects of various antagonists on withdrawal symptoms and LC activity.
Main Results:
- Morphine withdrawal activates LC neurons via non-N-methyl-D-aspartate (NMDA) pathways.
- Excitatory amino acid projections, potentially from the nucleus paragigantocellularis, contribute to LC activation.
- Intrinsic G-protein/cyclic AMP system changes in LC cells may modulate afferent input effects.
- NMDA antagonists reduce withdrawal behaviors without blocking LC hyperactivity, unlike clonidine.
Conclusions:
- Non-NMDA pathways are primary mediators of LC activation during opiate withdrawal.
- Competitive NMDA antagonists show promise for treating opiate withdrawal symptoms in humans.
- Non-competitive NMDA antagonists may have significant side effects, limiting their clinical use.