Examination of the metabolite hydroxybupropion in the reinforcing and aversive stimulus effects of nicotine in rats
| Autor: | Emma M. Malcolm, M. I. Damaj, Mohammed Shoaib, F. I. Carroll, Bruce E. Blough |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Nicotine medicine.medical_treatment Metabolite Self Administration Pharmacology Receptors Nicotinic chemistry.chemical_compound Reward medicine Avoidance Learning Animals Bupropion Hydroxybupropion Tobacco Use Disorder Antidepressive Agents Rats chemistry Antidepressant Smoking cessation Smoking Cessation Aversive Stimulus Self-administration Psychology medicine.drug |
| Zdroj: | Psychopharmacology. 232(15) |
| ISSN: | 1432-2072 |
| Popis: | Preclinical studies with bupropion in rodent models of nicotine dependence have generated equivocal findings with regard to translating the clinical efficacy of the antidepressant as a smoking cessation agent.Given that rats are poor metabolizers of bupropion, the present experiments examined (2S,3S)-hydroxybupropion, the major active metabolite, on the positive reinforcing and aversive stimulus properties of nicotine in rats.In male hooded Lister rats, (2S,3S)-hydroxybupropion (1.0-10.0 mg/kg IP) was tested on intravenous nicotine (0.03 mg/kg/inf) self-administration behaviour for three sessions (n = 8), and in another experiment, the same doses of (2S,3S)-hydroxybupropion were tested in a conditioned taste aversion procedure to assess the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake.(2S,3S)-hydroxybupropion attenuated nicotine intake in a manner similar to that produced by mecamylamine pretreatment (1.0 mg/kg SC). This effect on nicotine-taking was specific since these doses had no effect on responding maintained by sucrose presented orally (200 μl of 5 % w/v). (2S,3S)-hydroxybupropion (1, 3 and 10 mg/kg IP) pretreatment failed to modify the aversive effects produced by a small dose of nicotine (0.1 mg/kg SC).These results demonstrate this metabolite to specifically modify the positive reinforcing effects of nicotine without affecting its aversive motivational effects. We propose that the clinical efficacy of bupropion may be due to a combination of effects produced by bupropion and/or its active metabolite (2S,3S)-hydroxybupropion involving the inhibition of reuptake of dopamine and noradrenaline in reward centres of the brain and the noncompetitive antagonism of neuronal nicotinic receptors. |
| Databáze: | OpenAIRE |
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