title: 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 microg/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.
authors: Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcântara Gomes, Centro Biomédico, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. yael_a_v@yahoo.com.br
authors: Yael
authors: Y
authors: Abreu-Villaça
authors: Fernanda
authors: F
authors: Nunes
authors: Fabíola
authors: F
authors: do E Queiroz-Gomes
authors: Alex C
authors: AC
authors: Manhães
authors: Cláudio C
authors: CC
authors: Filgueiras
mesh_terms: D000375:Aging / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004326:Drinking / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000009:adverse effects* / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
chemical_list: D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D000431:Ethanol; D009538:Nicotine