Article

Tobacco smoke exposure induces nicotine dependence in rats

Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Dr., PO Box 100256, Gainesville, FL 32610, USA.
Psychopharmacology (Impact Factor: 3.99). 11/2009; 208(1):143-58. DOI: 10.1007/s00213-009-1716-z
Source: PubMed

ABSTRACT Tobacco smoke contains nicotine and many other compounds that act in concert on the brain reward system. Therefore, animal models are needed that allow the investigation of chronic exposure to the full spectrum of tobacco smoke constituents.
The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats.
The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Somatic signs were recorded from a checklist of nicotine abstinence signs. Nicotine self-administration sessions were conducted to investigate if tobacco smoke exposure affects the motivation to self-administer nicotine. Nicotinic receptor autoradiography was used to investigate if exposure to tobacco smoke affects central alpha7 nicotinic acetylcholine receptor (nAChR) and non-alpha7 nAChR levels (primarily alpha4beta2 nAChRs).
The nAChR antagonist mecamylamine dose-dependently elevated the brain reward thresholds of the rats exposed to tobacco smoke and did not affect the brain reward thresholds of the untreated control rats. Furthermore, mecamylamine induced more somatic withdrawal signs in the smoke-exposed rats than in the control rats. Nicotine self-administration was decreased 1 day after the last tobacco smoke exposure sessions and was returned to control levels 5 days later. Tobacco smoke exposure increased the alpha7 nAChR density in the CA2/3 area and the stratum oriens and increased the non-alpha7 nAChR density in the dentate gyrus.
Tobacco smoke exposure leads to nicotine dependence as indicated by precipitated affective and somatic withdrawal signs and induces an upregulation of nAChRs in the hippocampus.

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    • "From days 4 to 14, the average total suspended particulate matter was about 100 mg/m 3 and the CO level about 350 ppm. A previous study by our laboratory demonstrated that these tobacco smoke exposure conditions led to nicotine dependence in rats and plasma nicotine levels of approximately 45 ng/ml and cotinine levels of 250 ng/ml (Small et al., 2010). "
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    • "These preparations contain all compounds that potentially act upon neuronal activity. Tobacco smoke exposure activates DA neurons (Fa et al, 2000) and induces nicotine dependence (Small et al, 2010) in rats. ToEs and SmEs have been widely used to investigate the genotoxicity (for review, see DeMarini (2004)) and cytotoxicity (Bagchi et al, 1998, 1999; Tanaka et al, 2007; Yildiz et al, 1999) of tobacco intake. "
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