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

Abstract

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.

• Authors: Mohammed Shoaib
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 188 Issue 2 Pg. 252-7 (Oct 2006) ISSN: 0033-3158 [Print] Germany
• PMID: 16932923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nicotinic Agonists
• Receptors, Nicotinic
• isoarecolone
• Arecoline
• Nicotine

Topics

• Animals
• Arecoline (analogs & derivatives, pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Male
• Nicotine (administration & dosage)
• Nicotinic Agonists (pharmacology, therapeutic use)
• Rats
• Rats, Inbred Strains
• Receptors, Nicotinic (metabolism)
• Self Administration
• Tobacco Use Disorder (drug therapy, metabolism)