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Prodynorphin, proenkephalin and kappa opioid receptor mRNA responses to acute "binge" cocaine
R Spangler1, Y Zhou, C E Maggos
1Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA.
Abstract:
Previous studies showed that preprodynorphin (ppDyn) mRNA increases in caudate-putamen while kappa opioid receptor (KOR) mRNA decreases in substantia nigra after 3 and 14 days "binge" cocaine. To further characterize opioid mRNA responses, rats were administered: saline; 1 day cocaine followed by 1 day saline; 1 day cocaine; or 2 days cocaine. ppDyn mRNA in caudate-putamen increased in both groups receiving cocaine on the final day compared to groups receiving saline. Preproenkephalin (ppEnk) mRNA in caudate-putamen increased, and KOR mRNA in substantia nigra decreased, after 2 days of cocaine. Thus ppDyn mRNA is elevated acutely by cocaine, while ppEnk and KOR mRNAs show a significant response only on the second day of "binge" cocaine.
Insights
Cocaine use acutely elevates preprodynorphin (ppDyn) mRNA in the brain. However, preproenkephalin (ppEnk) mRNA and kappa opioid receptor (KOR) mRNA levels only significantly change after two days of cocaine exposure.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Previous research indicates that binge cocaine exposure alters opioid mRNA levels in specific brain regions.
- Preprodynorphin (ppDyn) mRNA increases in the caudate-putamen, and kappa opioid receptor (KOR) mRNA decreases in the substantia nigra after 3 and 14 days of cocaine use.
Purpose of the Study:
- To investigate the temporal dynamics of opioid mRNA expression in response to varying durations of cocaine administration.
- To further characterize the acute and sub-acute effects of cocaine on ppDyn, preproenkephalin (ppEnk), and KOR mRNA levels.
Main Methods:
- Rats were administered different cocaine regimens: saline, one day cocaine followed by one day saline, one day cocaine, or two days cocaine.
- Quantitative analysis of ppDyn mRNA in the caudate-putamen and KOR mRNA in the substantia nigra was performed.
Main Results:
- ppDyn mRNA in the caudate-putamen increased in rats receiving cocaine on the final day of administration compared to saline controls.
- Preproenkephalin (ppEnk) mRNA in the caudate-putamen and KOR mRNA in the substantia nigra showed significant changes only after two consecutive days of cocaine exposure.
- These findings suggest differential temporal responses of opioid mRNAs to cocaine.
Conclusions:
- Cocaine acutely elevates ppDyn mRNA levels in the caudate-putamen.
- A significant response in ppEnk mRNA and KOR mRNA requires at least two days of cocaine exposure, indicating a delayed effect.
- These results contribute to understanding the neuroadaptive changes in the opioid system during early stages of cocaine use.