Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal

Abstract

Smoking and consumption of alcoholic beverages are frequently associated during adolescence. This association could be explained by the cumulative behavioral effects of nicotine and ethanol, particularly those related to anxiety levels. However, despite epidemiological findings, there have been few animal studies of the basic neurobiology of the combined exposure in the adolescent brain. In the present work we assessed, through the use of the elevated plus maze, the short-and long-term anxiety effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (from the 30th to the 45th postnatal day) in four groups of male and female C57BL/6 mice: (1) Concomitant NIC (nicotine free-base solution (50 mg/ml) in 2% saccharin to drink) and ETOH (ethanol solution (25%, 2 g/kg) i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) Vehicle. C57BL/6 mice were selected, in spite of the fact that they present slower ethanol metabolism, because they readily consume nicotine in the concentration used in the present study. During exposure (45th postnatal day: PN45), our results indicated that ethanol was anxiolytic in adolescent mice and that nicotine reverted this effect. Short-term drug withdrawal (PN50) elicited sex-dependent effects: exposure to nicotine and/or ethanol was anxiogenic only for females. Although neither nicotine nor ethanol effects persisted up to 1 month postexposure (PN75), the coadministration elicited an anxiogenic response. In spite of the fact that generalizations based on the results from a single strain of mice are prone to shortcomings, our results suggest that the deficient response to the anxiolytic effects of ethanol in adolescents co-exposed to nicotine may drive higher ethanol consumption. Additionally, increased anxiety during long-term smoking and drinking withdrawal may facilitate relapse to drug use.

Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring

“…Regarding total chow consumption, the rANOVA indicated a significant Group × Day interaction [F = 4.7 (3,53), p = 0.05]. Pairwise comparisons indicated that food intake, either when considering the standard chow or the two chows (HSD and HFD) used for the selfselection diet, was not affected by nicotine exposure.…”

“…Since nicotine is considered the main psychoactive component of tobacco smoke that causes dependence [18,27], experimental models based on nicotine exposure during development should be useful to study the short-and long-term behavioral consequences of early tobacco smoke exposure ( [4],; [3,69]). …”

Effect of Aripiprazole on Anxiety Associated With Ethanol Physical Dependence and on Ethanol-Induced Place Preference

“…Several investigations have reported that long-term ethanol administration alters anxiety sensitivity in animals (3,4) and induces depression in humans (5). 5-HT 1A receptors are classified as G-protein-coupled receptors that are widely distributed in brain regions such as the frontal cortex, septum, amygdala, hippocampus, and hypothalamus, which receive serotonergic input from the raphe nuclei (59,60); and serotonergic activity modulates the diverse behavioral functions such as cognition and emotion through 5-HT 1A receptors (61).…”

“…Among the emotional behaviors and emotion-dependent behaviors that are considered to be modified by ethanol, the degree of anxiety and anxiety-related behaviors have been well reported as an emotional change by ethanol (3,4). Furthermore, functional relationship between alcohol dependence and depression has been supposed (5), and several investigators also demonstrated the co-morbidity of lifetime psychiatric disorder among alcoholic patients (6).…”

Environmental enrichment reverses memory impairment induced by toluene in mice

“…The study started on postnatal day 35 to 40 of the animals (PN 35 to 40). This stage was selected because mice at this age exhibit behavioral, neurochemical and endocrine patterns of human adolescent subjects (Abreu-Villaça et al, 2008;Burns and Proctor, 2012) and because this age is similar to the age of onset of inhalant abuse in humans . All animals were maintained under inverted controlled light-dark cycle conditions (12 h:12 h, lights on at 20:00 h) at 22 to 26 • C and had access to food and water ad libitum.…”