Mohammed Shoaib1, Nimish Sidhpura, Sajid Shafait. 1. Section of Behavioural Pharmacology, Institute of Psychiatry, Kings College London, De Crespigny Park, London SE5 8AF, UK. m.shoaib@iop.kcl.ac.uk
Abstract
RATIONALE: The clinical success of the antidepressant bupropion, marketed as Zyban in smoking cessation, presents an ideal opportunity to unravel its mechanism of action utilising animal models of nicotine dependence. OBJECTIVE: The present experiments utilise bupropion as a reference compound to examine putative interactions with stimulus properties of nicotine in rats. METHODS AND RESULTS: In male hooded Lister rats, bupropion (10 and 30 mg/kg IP) administered 30 min prior to each intravenous nicotine (0.03 mg/kg per infusion) self-administration session failed to attenuate rates of nicotine intake. Moreover, following the large dose of bupropion, nicotine intake was enhanced and response rates remained elevated throughout the 28-day course of treatment. To examine interactions with subjective effects of nicotine, rats trained to discriminate nicotine (0.2 mg/kg SC) from vehicle were tested with bupropion (1, 3, 10 and 30 mg/kg IP). Bupropion pre-treatment failed to exert a "nicotine-like" action and also failed to attenuate the orderly dose-related discrimination function of nicotine (0.05-0.4 mg/kg SC) in rats. Using the conditioned taste aversion procedure to assess the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake, bupropion (3, 10 and 30 mg/kg IP) pre-treatment failed to modify the aversive effects produced by a threshold dose of nicotine (0.2 mg/kg SC). CONCLUSIONS: The results obtained with bupropion in these animal models of dependence suggest this antidepressant may not directly interact with stimulus properties of nicotine; rather its clinical efficacy may be exposed in animal models that are based upon chronic exposure to nicotine and upon abstinence effects.
RATIONALE: The clinical success of the antidepressant bupropion, marketed as Zyban in smoking cessation, presents an ideal opportunity to unravel its mechanism of action utilising animal models of nicotine dependence. OBJECTIVE: The present experiments utilise bupropion as a reference compound to examine putative interactions with stimulus properties of nicotine in rats. METHODS AND RESULTS: In male hooded Lister rats, bupropion (10 and 30 mg/kg IP) administered 30 min prior to each intravenous nicotine (0.03 mg/kg per infusion) self-administration session failed to attenuate rates of nicotine intake. Moreover, following the large dose of bupropion, nicotine intake was enhanced and response rates remained elevated throughout the 28-day course of treatment. To examine interactions with subjective effects of nicotine, rats trained to discriminate nicotine (0.2 mg/kg SC) from vehicle were tested with bupropion (1, 3, 10 and 30 mg/kg IP). Bupropion pre-treatment failed to exert a "nicotine-like" action and also failed to attenuate the orderly dose-related discrimination function of nicotine (0.05-0.4 mg/kg SC) in rats. Using the conditioned taste aversion procedure to assess the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake, bupropion (3, 10 and 30 mg/kg IP) pre-treatment failed to modify the aversive effects produced by a threshold dose of nicotine (0.2 mg/kg SC). CONCLUSIONS: The results obtained with bupropion in these animal models of dependence suggest this antidepressant may not directly interact with stimulus properties of nicotine; rather its clinical efficacy may be exposed in animal models that are based upon chronic exposure to nicotine and upon abstinence effects.
Authors: F Scott Hall; Andre Der-Avakian; Thomas J Gould; Athina Markou; Mohammed Shoaib; Jared W Young Journal: Neurosci Biobehav Rev Date: 2015-06-06 Impact factor: 8.989
Authors: Jack E Henningfield; Tracy T Smith; Bethea A Kleykamp; Reginald V Fant; Eric C Donny Journal: Psychopharmacology (Berl) Date: 2016-10-21 Impact factor: 4.530