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Background: Although alcohol and nicotine are often used together, the biological consequences of these substances are not well understood. Identifying shared targets will inform cessation pharmacotherapies and provide a deeper understanding of how co-use of alcohol and nicotine impacts health, including biomarkers of stress and inflammation. Objective: We examined the effects of nicotine exposure and withdrawal on alcohol self-administration (SA), stress and inflammatory biomarkers, and a G-protein coupled receptor subunit (Gβ) in brain areas associated with drug use. Methods: Male rats were trained to SA alcohol and then received a nicotine pump ( n = 7-8 per group). We assessed alcohol intake for 12 days during nicotine exposure and then following pump removal to elicit withdrawal. After the behavioral studies, we assessed plasma leptin, corticosterone, and interleukin-1β (IL-1β), and Gβ protein expression in the amygdala, nucleus accumbens (NAc), and prefrontal cortex (PFC). Results: Nicotine exposure or withdrawal did not alter alcohol intake ( p > .05). Alcohol and nicotine withdrawal elevated corticosterone levels ( p = .015) and decreased Gβ levels in the PFC ( p = .004). In the absence of nicotine, alcohol SA suppressed IL-1β levels ( p = .039). Chronic exposure to nicotine or withdrawal during alcohol SA did not alter leptin levels or Gβ expression in the amygdala or NAc ( p's > .05). Conclusions: The combination of alcohol SA and nicotine withdrawal produced a persistent increase in stress biomarkers and a suppression in Gβ expression in the PFC, providing an important first step toward understanding the common biological mechanisms of alcohol/nicotine misuse.

Rationale: It is presently unclear whether diabetic rats experience greater rewarding effects of nicotine and/or negative affective states produced by nicotine withdrawal., Objective: The present study utilized a rodent model of diabetes to examine the rewarding effects of nicotine and negative affective states and physical signs produced by withdrawal., Methods: Separate groups of rats received systemic administration of either vehicle or streptozotocin (STZ), which destroys insulin-producing beta cells in the pancreas and elevates glucose levels. Place conditioning procedures were utilized to compare the rewarding effects of nicotine (conditioned place preference; CPP) and negative affective states produced by withdrawal (conditioned place aversion; CPA) in vehicle- and STZ-treated rats. CPA and physical signs of withdrawal were compared after administration of the nicotinic receptor antagonist mecamylamine to precipitate withdrawal in nicotine-dependent rats. A subsequent study utilized elevated plus maze (EPM) procedures to compare anxiety-like behavior produced by nicotine withdrawal in vehicle- and STZ-treated rats., Results: STZ-treated rats displayed greater rewarding effects of nicotine and a larger magnitude of aversive effects and physical signs produced by withdrawal as compared to vehicle-treated controls. STZ-treated rats also displayed higher levels of anxiety-like behavior on the EPM during nicotine withdrawal as compared to controls., Conclusion: The finding that both nicotine reward and withdrawal are enhanced in a rodent model of diabetes implies that the strong behavioral effects of nicotine promote tobacco use in persons with metabolic disorders, such as diabetes.