Details

Autor(en) / Beteiligte

• Anderson, S M
• Brunzell, D H

Titel

Anxiolytic‐like and anxiogenic‐like effects of nicotine are regulated via diverse action at β 2nicotinic acetylcholine receptors

Ist Teil von

• British journal of pharmacology, 2015-06, Vol.172 (11), p.2864-2877

Erscheinungsjahr

2015

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Background and Purpose Nicotine dose‐dependently activates or preferentially desensitizes β 2 subunit containing nicotinic ACh receptors ( β 2* nAChRs ). Genetic and pharmacological manipulations assessed effects of stimulation versus inhibition of β 2* nAChRs on nicotine‐associated anxiety‐like phenotype. Experimental Approach Using a range of doses of nicotine in β 2* nAChR subunit null mutant mice ( β 2 KO ; backcrossed to C 57 BL /6 J ) and their wild‐type ( WT ) littermates, administration of the selective β 2* nAChR agonist, 5 I ‐ A 85380, and the selective β 2* nAChR antagonist dihydro‐ β ‐erythroidine ( DHβE ), we determined the behavioural effects of stimulation and inhibition of β 2* nAChRs in the light–dark and elevated plus maze ( EPM ) assays. Key Results Low‐dose i.p. nicotine (0.05 mg·kg − 1) supported anxiolysis‐like behaviour independent of genotype whereas the highest dose (0.5 mg·kg −1 ) promoted anxiogenic‐like phenotype in WT mice, but was blunted in β 2 KO mice for the measure of latency. Administration of 5 I ‐ A 85380 had similar dose‐dependent effects in C57BL /6J WT mice; 0.001 mg·kg −1 5 I ‐ A 85380 reduced anxiety on an EPM , whereas 0.032 mg·kg −1 5 I ‐ A 85380 promoted anxiogenic‐like behaviour in both the light–dark and EPM assays. DHβE pretreatment blocked anxiogenic‐like effects of 0.5 mg·kg −1 nicotine. Similarly to DHβE , pretreatment with low‐dose 0.05 mg·kg −1 nicotine did not accumulate with 0.5 mg·kg −1 nicotine, but rather blocked anxiogenic‐like effects of high‐dose nicotine in the light–dark and EPM assays. Conclusions and Implications These studies provide direct evidence that low‐dose nicotine inhibits nAChRs and demonstrate that inhibition or stimulation of β 2* nAChRs supports the corresponding anxiolytic‐like or anxiogenic‐like effects of nicotine. Inhibition of β 2* nAChRs may relieve anxiety in smokers and non‐smokers alike.