Inhibition of monoamine oxidase isoforms modulates nicotine withdrawal syndrome in the rat

Abstract

AimsThere have been many reports of monoamine oxidase (MAO) inhibition by non-nicotine ingredients in tobacco smoke, persisting for days after smoking cessation. This study determined the effect of inhibiting MAO and its isoforms on nicotine withdrawal syndrome. Main methodsRats were rendered nicotine-dependent by seven days of subcutaneous (s.c.) 9mg/kg/day infusion of nicotine bitartrate. Twenty-two hours after termination of infusion, they were observed over 20min for somatically expressed nicotine withdrawal signs. Three hours before observation, rats were injected intraperitoneally (i.p.) with 4mg/kg each of the MAO A antagonist clorgyline and the MAO B antagonist deprenyl, or with saline alone. A similar experiment was performed with non-dependent, saline-infused rats. Another experiment compared nicotine-dependent rats that received injections of either saline or 4mg/kg clorgyline alone. A further experiment compared rats receiving either saline or 4mg/kg deprenyl alone. Key findingsCombined treatment with both MAO inhibitors markedly and significantly exacerbated somatically expressed nicotine withdrawal signs in nicotine infused rats, while having no significant effects in saline-infused rats. Rats injected s.c. with 4mg/kg clorgyline alone had significantly more withdrawal signs than saline-injected rats, while deprenyl-injected rats had significantly fewer signs than saline controls. Assays confirmed that clorgyline thoroughly reduced MAO A enzymatic activity and deprenyl thoroughly reduced MAO B activity. SignificanceThe results suggest that inhibition of MAO A may contribute to the intensity of withdrawal syndrome in smoking cessation.