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Updated: Jun 30, 2026
Spectral Confocal Imaging of Fluorescently tagged Nicotinic Receptors in Knock-in Mice with Chronic Nicotine Administration
Published on: February 10, 2012
Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout
S V Suarez1, A Amadon, E Giacomini
1Unité de Neurobiologie Intégrative du Système Cholinergique, URA CNRS 2182, Institut Pasteur, Département de Neuroscience, 25 rue du Dr. Roux, 75015 Paris, France.
Rationale:
The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity beta2-containing nicotinic receptors (beta2*nAChRs) are located.
Objectives:
We intend to see which brain circuits are activated when nicotine is given in animals naïve for nicotine and whether the beta2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas.
Materials And Methods:
We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and beta2 knockout (KO) mice.
Results:
Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, beta2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via alpha7 nicotinic receptors.
Conclusions:
Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on beta2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice.
Insights
Nicotine activates brain circuits via beta2* nicotinic receptors, counteracting anesthesia-induced decreases in brain activity. This study used fMRI to investigate nicotine
Area of Science:
- Neuroscience
- Pharmacology
- Neuroimaging
Background:
- Nicotine's behavioral effects are linked to beta2-containing nicotinic receptors.
- Nicotine-modulated behaviors involve multiple brain circuits containing high-affinity beta2-containing nicotinic receptors (beta2* nAChRs).
Purpose of the Study:
- To identify brain circuits activated by nicotine in naive animals.
- To determine if beta2* nAChRs are essential for nicotine's effect on the blood oxygen level dependent (BOLD) signal across all brain regions.
Main Methods:
- Functional magnetic resonance imaging (fMRI) was employed to measure brain activation.
- Nicotine (1 mg/kg) was administered to anesthetized C57BL/6J mice and beta2 knockout (KO) mice.
Main Results:
- Nicotine increased activation in frontal, motor, and somatosensory cortices, as well as the ventral tegmental area and substantia nigra.
- Anesthesia alone caused decreased BOLD signal in all brain structures.
- Beta2 KO mice did not show rescue from the anesthesia-induced BOLD signal decline, but nicotine activated meso-cortico-limbic circuits potentially via alpha7 nicotinic receptors.
Conclusions:
- Acute nicotine exposure, acting on beta2* nAChRs, compensates for anesthesia-induced decreases in brain activation within the meso-cortico-limbic network.
- The fMRI methodology is effective for comparing nicotine responses between wild-type and mutant mice.
