Alcohol-Induced Increases in Inflammatory Cytokines Are Attenuated by Nicotine in Region-Selective Manner in Male Rats

Olubukola Kalejaiye ； Bruk Getachew ； Clifford L. Ferguson ； Robert E. Taylor ； Yousef Tizabi

《Journal of Drug and Alcohol Research》 6期 (2017/12) Pp. 1-6-007

https://doi.org/10.4303/jdar/236036

摘要

Background. Heavy use of alcohol is commonly associated with heavy smoking (nicotine intake). Although many factors, including mood effects of these two drugs may contribute to their co-use, the exact neurobiological underpinnings are far from clear. It is well known that chronic alcohol exposure induces neuroinflammation that may precipitate depressive-like behavior, which is considered an important factor in alcohol relapse. Nicotine, on the other hand, possesses anti-inflammatory and antidepressant effects. Purpose. In this study, we sought to determine which proinflammatory markers may be associated with the depressogenic effects of chronic alcohol and whether nicotine pretreatment may normalize these changes. Study design. For this purpose, we treated adult maleWistar rats with alcohol (1.0 g/kg, IP), nicotine (0.3 mg/kg, IP) or their combination once daily for 14 days. Two prominent proinflammatory cytokines (IL-1β and TNF-α) in two primary brain regions, namely the hippocampus and frontal cortex that are intimately involved in mood regulation, were evaluated. Results. Chronic alcohol resulted in increases in both cytokines in both regions as determined by Western blot. Nicotine completely blocked alcohol-induced effects in the hippocampus, but not in the frontal cortex. These data suggest that nicotine may mitigate the inflammatory effects of alcohol in brain-selective region. Hence, the previously observed depressogenic effects of alcohol and the antidepressant effects of nicotine may at least be partially mediated through manipulations of proinflammatory cytokines in the hippocampus. Conclusion. These findings suggest possible therapeutic potential of anti-inflammatory cytokines in combating alcohol-induced depression and/or relapse.

關鍵字

alcoholism ； depression ； comorbidity ； cytokines ； IL-1β ； TNF-α ； hippocampus ； frontal cortex