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Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
Preprothyrotropin-releasing hormone mRNA in the rat central gray is strongly and persistently induced during morphine
1Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Abstract:
In vivo evidence strongly implicates the central gray in expression of the physical symptoms of opiate withdrawal. Preprothyrotropin-releasing hormone (ppTRH) mRNA is highly expressed in the central gray. Furthermore, systemic administration of thyrotropin-releasing hormone (TRH) inhibits the development of opiate dependence in rats. To elucidate the link between TRH and opiate withdrawal, we examined the regulation of ppTRH mRNA in the central gray of rats made dependent on morphine, and during opiate withdrawal, using quantitative in situ hybridization. In the ventrolateral central gray, a significant increase in ppTRH mRNA was observed 3 h after precipitation of withdrawal, and this increase persisted for 36 h. Upregulation of ppTRH mRNA was not seen with chronic morphine or acute naltrexone treatment alone and was specific for the ventrolateral central gray. These findings support a role for TRH or other ppTRH-derived peptides in the central gray during morphine withdrawal.
Insights
Thyrotropin-releasing hormone (TRH) plays a key role in the physical symptoms of opiate withdrawal. This study found increased preprothyrotropin-releasing hormone (ppTRH) mRNA in the central gray during morphine withdrawal in rats.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- The central gray region of the brain is implicated in the physical symptoms of opiate withdrawal.
- Preprothyrotropin-releasing hormone (ppTRH) mRNA is highly expressed in the central gray.
- Systemic administration of thyrotropin-releasing hormone (TRH) can inhibit the development of opiate dependence in rats.
Purpose of the Study:
- To investigate the relationship between TRH and opiate withdrawal.
- To examine the regulation of ppTRH mRNA in the central gray during morphine dependence and withdrawal.
Main Methods:
- Quantitative in situ hybridization was used to measure ppTRH mRNA levels.
- Rats were made dependent on morphine and subjected to withdrawal.
- Specific brain regions, particularly the ventrolateral central gray, were analyzed.
Main Results:
- A significant increase in ppTRH mRNA was observed in the ventrolateral central gray 3 hours after the onset of withdrawal, persisting for 36 hours.
- This upregulation was specific to the ventrolateral central gray and was not observed with chronic morphine or acute naltrexone treatment alone.
- These findings suggest a localized neurochemical change associated with withdrawal.
Conclusions:
- Thyrotropin-releasing hormone (TRH) or its derived peptides may play a significant role in the central gray during morphine withdrawal.
- The ventrolateral central gray is a key area involved in the neurobiological response to opiate withdrawal.
- Further research into TRH-related pathways could offer new therapeutic targets for managing opiate withdrawal symptoms.
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