Role of Rostromedial Tegmental Nucleus Afferents in Symptoms of Withdrawal from Chronic Ethanol Exposure

A significant number of individuals with alcohol use disorder struggle to maintain sobriety as a result of withdrawal symptoms including heightened pain sensitivity. Although common, the precise neural mechanisms underlying nociceptive symptoms of withdrawal are not well understood. The rostromedial tegmental nucleus (RMTg) is a GABAergic region that plays a critical role in avoidance behavior, aversive signaling, and pain modulation. Accumulating data provides evidence of RMTg hyperactivity during acute withdrawal and points to a role for the RMTg in regulating withdrawal symptoms. Yet, the role of this region in withdrawal-induced changes in pain sensitivity and the afferents that promote RMTg activity during acute withdrawal are unknown. In this thesis, I examined the role of RMTg afferents in regulating hyperalgesia during acute withdrawal. I found that thermal hyperalgesia emerged early after the cessation of ethanol exposure and persisted into protracted withdrawal. cFos expression, a marker of recent neuronal activity, was significantly increased in both the RMTg and RMTg-projecting lateral habenula (LHb) neurons during acute withdrawal. In vivo chemogenetic inhibition of this circuit attenuated withdrawal-induced thermal hyperalgesia in a sex-dependent manner. Collectively, these data suggest that RMTg-projecting LHb neurons play an important role in nociceptive symptoms of withdrawal from chronic ethanol exposure.

Author dc:creator

• Hyerim Yang (23292139)

• Withdrawal symptoms
• Alcohol use disorder

Statement dc:rights

• In Copyright
• Open Access after 2028-01-01

DOI dc:identifier

https://doi.org/10.25417/uic.31451890.v1

OAI identifier oai:identifier

oai:figshare.com:article/31451890