Nicotine Blocks the Depressogenic Effects of Alcohol: Implications for Drinking-Smoking Co-Morbidity

Abstract

Alcohol and nicotine are two very commonly abused legal substances. Although various hypotheses for such co-dependence have been suggested, it is not known whether the effects of alcohol and nicotine on mood behavior may also contribute to such co-abuse. Chronic exposure to high alcohol levels may lead to various neurochemical changes and precipitate depressive-like behavior. Nicotine, on the other hand, may exert an antidepressant-like effect. Here, we sought to determine whether nicotine may also block or mitigate the “depressogenic” effects of alcohol in a rat model. Moreover, since hippocampal brain-derived neurotrophic factor (BDNF) has been strongly implicated in mood regulation and effectiveness of antidepressants, the level of this neurotrophic factor in the hippocampus was also evaluated. Adult male Wistar rats were injected (i.p.) with alcohol (1.0 g/kg), nicotine (0.3 mg/kg) or their combination once daily for 14 days. Controls received saline. The behavior of these rats in open field locomotor activity (LMA), the forced swim test (FST), a measure of helplessness, and sucrose intake, a measure of anhedonia were evaluated 16–18 h after the last injection. Chronic alcohol did not affect LMA, but increased immobility in FST and decreased sucrose consumption, suggesting a “depressogenic” effect. Nicotine by itself did not affect any of the measured behavior but blocked alcohol-induced changes in FST and sucrose intake. Parallel to the behavioral changes, chronic alcohol resulted in a significant decrease in hippocampal BDNF, which was normalized by nicotine. These findings suggest that the opposing effects of alcohol and nicotine on depressive-like behavior may contribute to their co-abuse.

Effects of social deprivation on social and depressive-like behaviors and the numbers of oxytocin expressing neurons in rats

“…An observer who was blind to the experimental conditions of the animals scored each behavioral event as mobility if there were swimming or upward-directed climbing movements, and immobility was scored when there was a total lack of movement or the animal displayed only enough activity to keep its head above water. Behavioral observations from each 5-second epoch of the test were summated, and the percent immobility (# immobility events/total # events × 100) was calculated for each animal [39, 40]. …”

Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants

“…Conversely, alcohol preferring (AA) rats may exhibit depressive-like characteristics following voluntary alcohol intake compared to alcohol non-preferring (ANA) rats (Viglinskaya et al 1995). Although various theories have attempted to explain the association between AUD and depression, it appears that a number of factors, including genetic predisposition and alterations in neurochemical substrates, such as the noradrenergic system, may contribute to this co-morbidity (Balsamo et al, 2016; Bravo et al, 2017; Donadon and Osorio, 2016; Getachew et al, 2010; Jung et al, 2016; Kalejaye et al, 2013; Merikangas and Gelernter, 1990; Ovestreet et al, 2005; Rezvani et al, 2002, 2007; Rincon-Hoyos, et al, 2016). …”

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

“…This might be partially due to the very complex phenomenon of addiction as well as lack of full understanding of the pharmacodynamics of alcohol and nicotine. Nonetheless, it is evident that genetics, various receptor systems (including nicotinic cholinergic) as well as interactions of alcohol and nicotine with the neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), may play a significant role in their co-use [ 1 , 2 , 3 , 4 ]. In addition, some of the opposite pharmacological actions of these two substances, for example, sedative and depressogenic effects of alcohol [ 1 , 5 ], versus nicotine’s stimulant and antidepressant effects [ 5 , 6 , 7 ] are likely to entice the heavy drinker to smoke in order to counter some of the negative effect associated with high alcohol intake.…”

“…In addition, some of the opposite pharmacological actions of these two substances, for example, sedative and depressogenic effects of alcohol [ 1 , 5 ], versus nicotine’s stimulant and antidepressant effects [ 5 , 6 , 7 ] are likely to entice the heavy drinker to smoke in order to counter some of the negative effect associated with high alcohol intake. Indeed, we have provided evidence that the depressogenic effect of alcohol in rats can be blocked by nicotine [ 2 ]. Moreover, we and others have reported that the depressogenic effect of alcohol is associated with a reduction in the hippocampal BDNF [ 1 , 2 , 8 ], which was also reversed by nicotine [ 2 ].…”