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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
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Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine
Dusica Bajic1, Mariano Soiza-Reilly1, Allegra L Spalding2
1Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, United States of America; Department of Anaesthesia, Harvard Medical School, 25 Shattuck St., Boston, MA, 02115, United States of America.
Plos One
|February 4, 2015
Summary
Chronic morphine alters gene expression and increases cholinergic markers in the laterodorsal tegmental nucleus (LDTg). Nicotinic antagonists block morphine-induced locomotor sensitization, suggesting a role for cholinergic systems in opioid addiction.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Neuroplasticity in the mesolimbic dopaminergic system is key for opioid reward and addiction.
- Cholinergic transmission from the laterodorsal tegmental nucleus (LDTg) may influence these neuroplastic changes.
Purpose of the Study:
- To investigate if chronic morphine affects gene expression in the LDTg.
- To determine the role of cholinergic neurotransmission in morphine-induced behavioral adaptations.
Main Methods:
- Used rtPCR and a Neurotransmitters and Receptors PCR array to analyze gene expression changes in the LDTg after chronic morphine administration.
- Quantified vesicular acetylcholine transporter (VAChT) immunolabeling in LDTg neurons.
- Administered mecamylamine, a nicotinic antagonist, to assess its effects on locomotor sensitization, antinociception, tolerance, and dependence.
Main Results:
- Chronic morphine altered gene expression related to cholinergic neurotransmission in the LDTg.
- Morphine treatment significantly increased VAChT immunolabeling in LDTg neurons.
- Mecamylamine dose-dependently blocked locomotor sensitization to morphine but did not affect acute antinociception, tolerance, or dependence.
Conclusions:
- Endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine.
- Cholinergic neurons within the LDTg are implicated in this sensitization process.
- Targeting these cholinergic pathways may offer novel strategies for treating opioid addiction.
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