Tobacco smoke exposure induces nicotine dependence in rats.
BACKGROUND
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.


OBJECTIVE
The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Small
Elysia
E
Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Dr., PO Box 100256, Gainesville, FL 32610, USA.
Shah
Hina P
HP
Davenport
Jake J
JJ
Geier
Jacqueline E
JE
Yavarovich
Kate R
KR
Yamada
Hidetaka
H
Sabarinath
Sreedharan N
SN
Derendorf
Hartmut
H
Pauly
James R
JR
Gold
Mark S
MS
Bruijnzeel
Adrie W
AW
D000818:Animals; D001345:Autoradiography; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D009042:Motivation; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012646:Self Administration; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014029:Tobacco Use Disorder / Q000209:etiology*; D015854:Up-Regulation / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D014028:Tobacco Smoke Pollution; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008464:Mecamylamine; D009538:Nicotine