Investigating the actions of bupropion on dependence-related effects of nicotine in rats.
BACKGROUND
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.


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.
Shoaib
Mohammed
M
Section of Behavioural Pharmacology, Institute of Psychiatry, Kings College London, De Crespigny Park, London SE5 8AF, UK. m.shoaib@iop.kcl.ac.uk
Sidhpura
Nimish
N
Shafait
Sajid
S
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D016642:Bupropion / Q000627:therapeutic use*; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D012016:Reference Values; D014029:Tobacco Use Disorder / Q000188:drug therapy*
D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D009538:Nicotine