Differential expression of the beta4 neuronal nicotinic receptor subunit affects tolerance development and nicotinic binding sites following chronic nicotine treatment.

ABSTRACT: The role of neuronal nicotinic acetylcholine receptors (nAChR) containing the β4 subunit in tolerance development and nicotinic binding site levels following chronic nicotine treatment was investigated. Mice differing in expression of the β4-nAChR subunit [wild-type (β4(++)), heterozygote (β4(+-)) and null mutant (β4(--))] were chronically treated for 10 days with nicotine (0, 0.5, 1.0, 2.0 or 4.0mg/kg/h) by constant intravenous infusion. Chronic nicotine treatment elicited dose-dependent tolerance development. β4(--) mice developed significantly more tolerance than either β4(++) or β4(+-) mice which was most evident following treatment with 4.0mg/kg/h nicotine. Subsets of [(125)I]-epibatidine binding were measured in several brain regions. Deletion of the β4 subunit had little effect on i

SUBMITTER: Meyers EE 

PROVIDER: S-EPMC4336781 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature