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Receptor systems involved in self‐administration of the tobacco smoke constituent, norharmane, alone and combined with nicotine
Author(s) -
Arnold Monica M,
Perez Jessica M,
Belluzzi James D,
Leslie Frances M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.765.8
Subject(s) - nicotine , pharmacology , medicine , tobacco smoke , smoking cessation , bupropion , self administration , addiction , (+) naloxone , mecamylamine , anesthesia , receptor , nicotinic agonist , opioid , psychiatry , environmental health , pathology
Cigarette smoking is the leading cause of preventable death in the U.S., with low cessation rates. Although drugs that decrease responding in the nicotine self‐administration (SA) model have been marketed as cessation aids for smoking, they have limited efficacy. Their minimal usefulness despite success in animal studies could be because the SA model does not include other tobacco smoke constituents, which may interact with nicotine to create tobacco addiction. Previously, we have shown that the monoamine oxidase inhibitor and tobacco smoke constituent, norharmane is self‐administered alone and increased reinforced responding when combined with nicotine. The aim of the present study was to determine the mechanisms underlying SA of nicotine (nic), norharmane (NH) and the combination (nicNH). Adult male rats were allowed to self‐administer (i.v.) nic (7.5 μg/kg/inj), NH (2.5 μg/kg/inj) or nicNH (7.5+2.5 μg/kg/inj) for 12 days at FR1. Once baseline responding occurred, rats received a 15‐minute pretreatment (s.c.) of mecamylamine (0.75–3.0 mg/kg), ketanserin (0.5–2 mg/kg) or naloxone (0.75– 5.0 mg/kg) prior to SA. Preliminary results indicate that different receptor systems contribute to NH and nic reinforcement. These data suggest that inclusion of other constituents when testing drugs as potential cessation aids may yield more efficacious treatments.