Effects of prazosin, clonidine, and propranolol on the elevations in brain reward thresholds and somatic signs associated with nicotine withdrawal in rats

Adrie W. Bruijnzeel, Mahendra Bishnoi, Irma A. Van Tuijl, Kim F.M. Keijzers, Kate R. Yavarovich, Tim M. Pasek, Jenna Ford, Jon C. Alexander, Hidetaka Yamada

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Rationale Tobacco withdrawal is characterized by a negative mood state and relatively mild somatic symptoms. Increased noradrenergic transmission has been reported to play an important role in opioid withdrawal, but little is known about the role of noradrenergic transmission in nicotine withdrawal. Objectives The aim of these experiments was to investigate the effects of prazosin, clonidine, and propranolol on the negative mood state and somatic signs associated with nicotine withdrawal in rats. Methods A discrete-trial intracranial self-stimulation procedure was used to assess the negative affective state of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. Results In all the experiments, the nicotinic acetylcholine receptor antagonist mecamylamine (3 mg/kg) elevated the brain reward thresholds of the nicotine-treated rats and did not affect those of the control rats. The a1-adrenergic receptor antagonist prazosin (0.0625 and 0.125 mg/kg) dosedependently attenuated the elevations in brain reward thresholds associated with precipitated nicotine withdrawal. The α2-adrenergic receptor agonist clonidine (10-40 μg/kg) andthe nonselective β-adrenergic receptor antagonist propranolol (2.5-10 mg/kg) did not attenuate the elevations in brain reward thresholds associated with nicotine withdrawal. Furthermore, mecamylamine (2 mg/kg) inducedmore somatic signs in the nicotine-treated rats than in the control rats. Clonidine and propranolol, but not prazosin, decreased the total number of somatic signs associated with nicotine withdrawal. Conclusion Blockade of a1-adrenergic receptors attenuates the deficit in brain reward function associated with nicotine withdrawal. Antagonism of β-adrenergic receptors or stimulation of α2-adrenergic receptors attenuates the somatic symptoms of nicotine withdrawal.

Original languageEnglish (US)
Pages (from-to)485-499
Number of pages15
JournalPsychopharmacology
Volume212
Issue number4
DOIs
StatePublished - Dec 2010

Keywords

  • Adrenergic receptors
  • Brain reward function
  • Clonidine
  • Nicotine
  • Norepinephrine
  • Prazosin
  • Propranolol
  • Rats
  • Withdrawal

ASJC Scopus subject areas

  • Pharmacology

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