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NMDA antagonists and clonidine block c-fos expression during morphine withdrawal
K Rasmussen1, M Brodsky, C E Inturrisi
1Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Synapse (New York, N.Y.)
|May 1, 1995
Summary
Naltrexone-precipitated morphine withdrawal increases c-fos mRNA in specific brain regions. NMDA receptor antagonists and clonidine partially block these changes, revealing pathways involved in opioid withdrawal.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- The c-fos gene is a marker for neuronal activation in the central nervous system (CNS).
- Opioid withdrawal, induced by naltrexone in morphine-dependent rats, triggers c-fos expression in specific brain areas.
- NMDA receptor antagonists and clonidine are known to reduce withdrawal severity.
Purpose of the Study:
- To investigate the neuroanatomical localization of c-fos mRNA changes during naltrexone-precipitated morphine withdrawal.
- To determine the effects of NMDA receptor antagonists (MK801, LY274614) and clonidine on c-fos mRNA expression during withdrawal.
Main Methods:
- Measuring c-fos mRNA levels using solution hybridization in various brain regions of control and morphine-dependent rats.
- Administering saline, MK801, LY274614, or clonidine before naltrexone challenge.
Main Results:
- Morphine treatment elevated c-fos mRNA in the striatum (STR) and amygdala (AMY).
- Naltrexone increased c-fos mRNA in the nucleus accumbens (NA), frontal cortex (FC), amygdala (AMY), and hippocampus (HIP) of dependent rats.
- MK801 blocked naltrexone-induced c-fos in AMY; LY274614 and clonidine blocked it in AMY and NA.
Conclusions:
- These findings map neuroanatomical pathways involved in morphine withdrawal.
- The study identifies the sites of action for compounds that alleviate opioid withdrawal symptoms.