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Effects of isoarecolone, a nicotinic receptor agonist in rodent models of nicotine dependence

Lookup NU author(s): Dr Mohammed Shoaib


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Rationale: The nicotinic receptor agonist, isoarecolone, has 'nicotine-like' subjective properties as detected by rats in a discrimination paradigm. However, isoarecolone lacks the intra-accumbens dopamine-releasing effects, a feature akin to most abused substances. In the five-choice serial reaction time task, isoarecolone can enhance attention and thus may be developed as a cognitive enhancer. Objective: The present experiments assess the dependence profile of isoarecolone in rodent models of nicotine dependence. Method and results: Tests for cross-substitution in which isoarecolone is substituted for nicotine [0.3 mg/kg/infusion (inf)] self-administration suggest isoarecolone to have nominal reinforcing properties (0.3 or 1.0 mg/kg/inf); intake of isoarecolone declined over three test sessions in which responding was no different from saline extinction, and behaviour was reinstated by re-presenting nicotine. In a model of nicotine-seeking behaviour, rats having been extinguished by removal of nicotine (0.03 mg/kg/inf) and associated cues, the presentation of priming doses of nicotine (0.1-0.4 mg/kg s.c.) with the cues robustly reinstated responding of nicotine-seeking behaviour. Tests with priming doses of isoarecolone (1-20 mg/kg s.c.) shown previously to generalise to nicotine in discrimination tests produced significant levels of reinstatement but the responses were significantly less compared to nicotine-induced reinstatement. Conclusion: Overall, these results suggest that isoarecolone with its unique profile of behavioural activity should be further examined for treating chronic diseases that are characterised by attentional dysfunction. © Springer-Verlag 2006.

Publication metadata

Author(s): Shoaib M

Publication type: Article

Publication status: Published

Journal: Psychopharmacology

Year: 2006

Volume: 188

Issue: 2

Pages: 252-257

ISSN (print): 0033-3158

ISSN (electronic): 1432-2072

Publisher: Springer


DOI: 10.1007/s00213-006-0498-9


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