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


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.


CONCLUSIONS
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.
Shoaib
Mohammed
M
Psychobiology Research Laboratories, Newcastle Medical School, Newcastle University, Newcastle, NE2 4HH, UK. mohammed.shoaib@newcastle.ac.uk
D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D009538:Nicotine / Q000008:administration & dosage; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000378:metabolism
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C095493:isoarecolone; D001115:Arecoline; D009538:Nicotine