title: Nicotine and ethanol interact during adolescence: effects on the central cholinergic systems.
abstract: Co-occurrence of tobacco smoking and alcohol consumption during adolescence is frequent and well documented. However, little is known about the basic neurobiology of the combined exposure in the adolescent brain. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChRs), the current work focused on cholinergic systems. From the 30th to the 45th postnatal day (PN), C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: 1) concomitant NIC (50 microg/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; 2) NIC exposure; 3) ETOH exposure; 4) vehicle. We assessed nAChR binding, choline acetyltransferase (ChAT) activity and [3H]hemicholinium-3 (HC-3) binding in the cerebral cortex and midbrain of mice on PN45. In the cortex, ETOH had no effect on nAChRs. In contrast, NIC produced nAChR upregulation while NIC+ETOH elicited a more pronounced effect. In the midbrain, neither ETOH nor NIC had effects on nAChRs. NIC+ETOH, however, elicited a robust nAChR upregulation. Regarding ChAT activity, treatment effects differed between males and females in the cortex. Male NIC mice presented an increase in ChAT. However, ETOH reversed this effect. In contrast, female NIC mice presented decreased ChAT activity. In the midbrain, ETOH increased ChAT. HC-3 binding was not affected. These results indicate that the central cholinergic system is a site at which nicotine and ethanol interact. This interaction might underlie the association between tobacco and alcohol consumption during adolescence.
authors.affiliation: 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, RJ, 20550-170, Brazil.
authors.forename: Anderson
authors.initials: A
authors.lastname: Ribeiro-Carvalho
authors.forename: Carla S
authors.initials: CS
authors.lastname: Lima
authors.forename: Cláudio C
authors.initials: CC
authors.lastname: Filgueiras
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.forename: Yael
authors.initials: Y
authors.lastname: Abreu-Villaça
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000254:growth & development; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006426:Hemicholinium 3 / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D017729:Presynaptic Terminals / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002492:Central Nervous System Depressants; D018678:Cholinergic Agents; D026901:Membrane Transport Proteins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; C065637:choline transporter; D006426:Hemicholinium 3; D000431:Ethanol; D009538:Nicotine; D002795:Choline O-Acetyltransferase