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

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Abstract

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 (β2*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 β2*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 β2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice.

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Acknowledgments

This research was supported by the Association pour la Recherche sur les Nicotinanées, which provided a grant to S. Granon and a post-doc grant for S. Suarez. S. Granon was also supported by an ANR grant. D. LeBihan was supported by a grant from the cancéropôle d’Ile-de-France. The Pasteur Institute (Paris), the CNRS, and the CEA also contributed to this work. The authors thank Gilles Bonvento and Vincent Lebon for their help in the setup of the experiments; Uwe Maskos, Philippe Faure, and Arnaud Cressant for comments on the manuscript; and two anonymous referees for their constructive reading and suggestions.

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Authors and Affiliations

  1. Unité de Neurobiologie Intégrative du Système Cholinergique, URA CNRS 2182, Institut Pasteur, Département de Neuroscience, 25 rue du Dr. Roux, 75015, Paris, France

    S. V. Suarez, J.-P. Changeux & S. Granon

  2. Service Hospitalier Frédéric Joliot, 4 place du général Leclerc, 91400, Orsay, France

    A. Amadon, E. Giacomini & D. Le Bihan

  3. Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    A. Wiklund

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  1. S. V. Suarez
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  2. A. Amadon
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  3. E. Giacomini
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  4. A. Wiklund
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  5. J.-P. Changeux
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  6. D. Le Bihan
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  7. S. Granon
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Correspondence to S. Granon.

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Suarez, S.V., Amadon, A., Giacomini, E. et al. Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study. Psychopharmacology 202, 599–610 (2009). https://doi.org/10.1007/s00213-008-1338-x

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  • DOI: https://doi.org/10.1007/s00213-008-1338-x

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