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 μg/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.
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Acknowledgements
This work was supported by grants from Philip Morris USA Inc. and Philip Morris International, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-BRAZIL), and by fellowships from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ-BRAZIL) and Sub-reitoria de Pós-graduação e Pesquisa da Universidade do Estado do Rio de Janeiro (SR2-UERJ). We are thankful to Armando Meyer for helpful comments and to Edson Oliveira for animal care.
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None of the authors receive personal compensation from Philip Morris USA Inc. and Philip Morris International. Furthermore, the agreement between the authors and Philip Morris USA Inc. and Philip Morris International strongly encourages the publication of results in the open scientific literature, without prior restrictions or consultation. The authors have no other conflicts of interest to declare.
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Abreu-Villaça, Y., Nunes, F., do E Queiroz-Gomes, F. et al. Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal. Neuropsychopharmacol 33, 599–610 (2008). https://doi.org/10.1038/sj.npp.1301429
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