Involvement of alpha1-adrenergic receptors in tranylcypromine enhancement of nicotine self-administration in rat.

CIGARETTE smokers; NICOTINE; MONOAMINE oxidase; AMINE oxidase; NEUROTRANSMITTERS; DOPAMINE

The mechanisms mediating tobacco addiction remain elusive. Nicotine, the psychoactive component in tobacco, is generally believed to be the main cause of reward and addiction. However, tobacco smoke contains thousands of constituents, some of which may interact with nicotine to enhance reward. It has previously been shown that monoamine oxidase (MAO) inhibition, known to result from smoking, can enhance nicotine self-administration. The aim of the present study was to evaluate the role of noradrenergic systems in mediating this enhancement of nicotine reward. The objective of this study was to test the hypothesis that MAO inhibitor pretreatment enhances nicotine self-administration by activation of noradrenergic pathways that regulate dopamine release in the nucleus accumbens (NAc). The effect of prazosin (0.0625–0.5 mg/kg, i.p.), a specific α1-adrenergic receptor antagonist, was examined on male rats pretreated with tranylcypromine (3 mg/kg), an irreversible inhibitor of MAO A and B. Acquisition of nicotine (10 μg kg−1 inj−1, i.v.) self-administration behavior was examined over a 5-day period. Nicotine (60 μg kg−1 inj−1, i.v.)-induced increase in NAc extracellular dopamine levels was examined by in vivo microdialysis in non-self-administering animals. We have shown that (1) tranylcypromine enhances nicotine self-administration, (2) prazosin pretreatment blocks both the acquisition and the expression of nicotine self-administration, and (3) prazosin pretreatment diminishes nicotine-induced dopamine release in the NAc. These data indicate that the stimulation of α1-adrenergic receptors is critical for tranylcypromine enhancement of nicotine reward and suggest a critical interplay between the noradrenergic and dopaminergic systems in tobacco addiction. [ABSTRACT FROM AUTHOR]

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