Vulnerability to nicotine self-administration in adolescent mice correlates with age-specific expression of α4* nicotinic receptors.
The majority of smokers begin during adolescence, a developmental period with a high susceptibility to substance abuse. Adolescents are affected differently by nicotine compared to adults, with adolescents being more vulnerable to nicotine's rewarding properties. It is unknown if the age-dependent molecular composition of a younger brain contributes to a heightened susceptibility to nicotine addiction. Nicotine, the principle pharmacological component of tobacco, binds and activates nicotinic acetylcholine receptors (nAChRs) in the brain. The most prevalent is the widely expressed α4-containing (α4*) subtype which mediates reward and is strongly implicated in nicotine dependence. Exposing different age groups of mice, postnatal day (P) 44-86 days old, to a two bottle-choice oral nicotine self-administration paradigm for five days yielded age-specific consumption levels. Nicotine self-administration was elevated in the P44 group, peaked at P54-60 and was drastically lower in the P66 through P86 groups. We also quantified α4* nAChR expression via spectral confocal imaging of brain slices from α4YFP knock-in mice, in which the α4 nAChR subunit is tagged with a yellow fluorescent protein. Quantitative fluorescence revealed age-specific α4* nAChR expression in dopaminergic and GABAergic neurons of the ventral tegmental area. Receptor expression showed a strong positive correlation with daily nicotine dose, suggesting that α4* nAChR expression levels are age-specific and may contribute to the propensity to self-administer nicotine.
Department of Biology, Centre for Biomedical Research, University of Victoria, Canada.
Anthony
A
Renda
Department of Biology, Centre for Biomedical Research, University of Victoria, Canada.
Nora
N
Penty
Department of Biology, Centre for Biomedical Research, University of Victoria, Canada.
Pragya
P
Komal
Department of Biology, Centre for Biomedical Research, University of Victoria, Canada. Electronic address: raad@uvic.ca.
Raad
R
Nashmi
D000367:Age Factors; D000818:Animals; D005260:Female; D015870:Gene Expression; D055879:Gene Knock-In Techniques; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000008:administration & dosage*; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000235:genetics*; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D009538:Nicotine; D011978:Receptors, Nicotinic
Mice; Nicotine addiction; Nicotine self-administration; Nicotinic acetylcholine receptors