A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.
The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar-Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil. Electronic address: yael_a_v@yahoo.com.br.
Yael
Y
Abreu-Villaça
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar-Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil.
Monique
M
Correa-Santos
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar-Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil.
Ana C
AC
Dutra-Tavares
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar-Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil.
Danielle
D
Paes-Branco
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar-Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil.
Andre
A
Nunes-Freitas
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar-Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil.
Alex C
AC
Manhães
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar-Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil.
Cláudio C
CC
Filgueiras
Departamento de Ciências, Faculdade de Formação de Professores da Universidade do Estado do Rio de Janeiro, Rua Dr. Francisco Portela 1470-Patronato, São Gonçalo, RJ 24435-005, Brazil.
Anderson
A
Ribeiro-Carvalho
D000105:Acetyl Coenzyme A / Q000493:pharmacokinetics; D000110:Acetylcholinesterase / Q000378:metabolism*; D000367:Age Factors; D000470:Alkaloids / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D001392:Azocines / Q000493:pharmacokinetics; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011807:Quinolizines / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012737:Sex Factors; D012906:Smoke / Q000009:adverse effects; D014316:Tritium / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000187:drug effects; D014026:Nicotiana; D000093843:Quinolizidine Alkaloids
D000105:Acetyl Coenzyme A; D000110:Acetylcholinesterase; D000470:Alkaloids; D001392:Azocines; D002247:Carbon Isotopes; D002795:Choline O-Acetyltransferase; D009538:Nicotine; D018722:Nicotinic Agonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; D012906:Smoke; D014316:Tritium; C004712:cytisine; D000093843:Quinolizidine Alkaloids
Cigarette; Denicotinized; Development; Drugs of abuse; Smoking; nAChR