Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study.
BACKGROUND
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.


OBJECTIVE
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.


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.
Suarez
S V
SV
Unité de Neurobiologie Intégrative du Système Cholinergique, URA CNRS 2182, Institut Pasteur, Département de Neuroscience, 25 rue du Dr. Roux, 75015 Paris, France.
Amadon
A
A
Giacomini
E
E
Wiklund
A
A
Changeux
J-P
JP
Le Bihan
D
D
Granon
S
S
D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants; D004867:Equipment Design; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging / Q000295:instrumentation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D013268:Stimulation, Chemical
D000697:Central Nervous System Stimulants; D009538:Nicotine; D018722:Nicotinic Agonists; D010100:Oxygen; D011978:Receptors, Nicotinic