Nicotine Self‐administration in Combination with the Tobacco Constituent, Norharmane

Abstract

Tobacco is one of the most abused drugs in today's society. Despite this, nicotine, the best characterized psychoactive component of tobacco is only weakly reinforcing in animals. A reason for this discrepancy may be that nicotine might act in concert with other components found in tobacco to create its addictive potential. There are over 4000 constituents found in cigarette smoke and of interest to the present study are those that inhibit the enzyme, monoamine oxidase (MAO). MAO activity has been shown to be decreased in the brains of smokers and it has been suggested that MAO inhibition may play a role in the reinforcing properties of cigarettes. In light of this, we have investigated the potential rewarding properties of nicotine in combination with norharmane (NH), a component of cigarette smoke known to inhibit MAO‐A and B reversibly. Preliminary data indicate that addition of NH (0.025 – 2.5 μg/kg/inj) to the i.v. solution supports acquisition and maintenance of self‐administration of a low dose of nicotine (7.5 μg/kg/inj) at an FR‐1 schedule without prior food training. An intermediate dose of NH (0.25 mg/kg/inj) supports continued self‐administration of nicotine as the task is made progressively harder through progressive ratio. Following extinction of self‐administration of nicotine/NH, drug‐seeking behavior can be reinstated by both cues and priming drug injection. These findings suggest that the addictive properties of cigarettes may result from the combined actions of nicotine and other tobacco constituents.