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

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Abstract

Rationale

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.

Objective

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).

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

This work was supported by PHS Grant DA21267 and a fellowship from TRDRP 13DT-0033 (S.L). Experiments comply with the current laws of the country in which they were performed. All experimental procedures were performed in compliance with NIH Guide for Care and Use of Laboratory Animals (NIH No 85-23, rev. 1985) and approved by the UCI Institutional Animal Care and Use Committee.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, University of California, Room 360, MS2, Irvine, CA, 92697, USA

    Anne-Sophie Villégier, James D. Belluzzi & Frances M. Leslie

  2. Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA, 92697, USA

    Shahrdad Lotfipour & Frances M. Leslie

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  1. Anne-Sophie Villégier
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  2. Shahrdad Lotfipour
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  3. James D. Belluzzi
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  4. Frances M. Leslie
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Correspondence to Anne-Sophie Villégier.

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Villégier, AS., Lotfipour, S., Belluzzi, J.D. et al. Involvement of alpha1-adrenergic receptors in tranylcypromine enhancement of nicotine self-administration in rat. Psychopharmacology 193, 457–465 (2007). https://doi.org/10.1007/s00213-007-0799-7

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