Emily Bian,Jiang-Hong Ye,Jing Li ,Michal Gajewski ,Nimisha Shiwalkar,Qing Fan,Qinghua Mei ,Rao Fu ,Wanhong Zuo ,Xiao Han, Pain, Anxiety- and Depression-Like Behaviors in Alcohol-Preferring and -NonPreferring Rats Neurology and Neurobiology 2020 2613-7828 http://dx.doi.org/10.31487/j.NNB.2020.02.05 https://www.sciencerepository.org/pain-anxiety-and-depression-like-behaviors-in-alcohol-preferring_NNB-2020-2-105 Abstract: Introduction: Psychiatric disorders such as anxiety, hyperalgesia, and depression have been associated with excessive alcohol drinking, but the neuronal mechanisms involved are only partially understood. Alcoholism more often occurs in individuals with a family history, indicating that genes may play a critical role. Chronic alcohol exposure alters calcium/calmodulin-dependent protein kinase II (CaMKII) signaling in the lateral habenula (LHb), and the LHb is implicated in mediating aversive behaviors, including those related to alcohol. We compared the CaMKII signaling in the LHb and the aberrant behaviors in the selectively bred alcohol-preferring (P) and alcohol-non-preferring (NP) lines of rats. Materials and Methods: The responses to mechanical (Von Frey) and thermal (Hargreaves) nociception tests, anxiety- (elevated plus maze, Marble burying) and depressive-like behaviors (forced swimming) were examined in the alcohol-naïve P and NP rats, as well as in P rats after 4-8 weeks of alcohol consumption; their LHb tissues were also collected for Western blot analysis of CaMKII expression. Results: Compared to NP rats, the P rats had a higher sensitivity to mechanical stimuli, and displayed depressive- and anxiety-like behaviors, as well as a higher level of CaMKII in the LHb. Alcohol consumption alleviated all these behaviors, except for anxiety, and decreased CaMKII levels in the LHb of P rats. Conclusions: The results show that selective breeding for different oral alcohol preference has produced differences in nociception, anxiety, and depression, as well as CaMKII expression in the LHb of P and NP rats. P rats may deal with pain and depression by self-medicating with alcohol.Keywords: Nociception, elevated plus maze, Hargreaves, Von Frey, marble burying, CaMKII