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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.
Sprache
Englisch
Identifikatoren
ISSN: 0007-1188
eISSN: 1476-5381
DOI: 10.1111/bph.13090
Titel-ID: cdi_crossref_primary_10_1111_bph_13090
Format
–
Weiterführende Literatur
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