title: Combined exposure to nicotine and ethanol in adolescent mice differentially affects memory and learning during exposure and withdrawal.
abstract: Human adolescents often associate tobacco smoking and consumption of alcoholic beverages. In spite of this frequent association, little is known about the basic neurobiology of the dual exposure in the adolescent brain. In the present work, we assessed, through the use of the step-through passive avoidance box (2mA, 2s; test-retest interval of 24h), short- and long-term memory/learning effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (postnatal days 30-45: PN30-45) in four groups of male and female C57BL/6 mice: (1) concomitant NIC [nicotine free base solution (50microg/ml) in 2% saccharin to drink] and ETOH [ethanol solution (25%, 2g/kg) i.p. injected every other day] exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. During exposure (PN44-45), deficits in memory/learning due to concomitant NIC+ETOH exposure reflected the summation of the two individual sets of effects. During a short-term drug withdrawal (PN49-50), nicotine improved memory/learning, however, ethanol blocked nicotine-induced improvements. One month post-exposure (PN74-75), a significant female-only improvement in memory/learning was observed as a result of co-administration. In conclusion, our results suggest that detrimental effects of nicotine and ethanol on memory/learning during adolescent combined exposure represent a worsened outcome from the dual exposure. However, negative effects of the combined exposure fail to persist during withdrawal. In fact, the combined exposure elicits a sex-dependent late onset beneficial effect on memory/learning during withdrawal.
authors.affiliation: Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Av. Prof. Manuel de Abreu 444, 5 andar, Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil. yael_a_v@yahoo.com.br
authors.forename: Yael
authors.initials: Y
authors.lastname: Abreu-Villaça
authors.forename: Ana H
authors.initials: AH
authors.lastname: Medeiros
authors.forename: Carla S
authors.initials: CS
authors.lastname: Lima
authors.forename: Felipe P
authors.initials: FP
authors.lastname: Faria
authors.forename: Cláudio C
authors.initials: CC
authors.lastname: Filgueiras
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D012737:Sex Factors; D018709:Statistics, Nonparametric
chemical_list: D002492:Central Nervous System Depressants; D004338:Drug Combinations; D018722:Nicotinic Agonists; D000431:Ethanol; D009538:Nicotine