ORIGINAL INVESTIGATION Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study S. V. Suarez & A. Amadon & E. Giacomini & A. Wiklund & J.-P. Changeux & D. Le Bihan & S. Granon Received: 14 May 2008 / Accepted: 10 September 2008 # Springer-Verlag 2008 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 somato- sensory 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. Howev- er, 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. Keywords Psychostimulant . Addiction . Dependence . Reward system . Anesthesia . Imaging Introduction Nicotine is a major addictive component of tobacco smoke and a strong psychostimulant. From a behavioral point of view, nicotine has been involved in multiple cognitive, emotional, and psychomotor processes, either after acute or chronic exposure, in human (Heishman et al. 1994; Newhouse et al. 2004; Xu et al. 2007), primate (Valette et al. 2007), or rodent models (e.g., Stolerman et al. 1973; Marks et al. 1985; Gäddnäs et al. 2000; Besson et al. 2007; for review, see Matta et al. 2007). It activates the release of several neurotransmitters (Li and Eisenach 2002; Rossi et al. 2005; Villégier et al. 2006; Fallon et al. 2007), stimulates dopaminergic neuron firing (Mameli-Engvall et al. 2006) and dopamine striatal release (Di Chiara 2000; Pietila and Psychopharmacology DOI 10.1007/s00213-008-1338-x S. V. Suarez : J.-P. Changeux : S. Granon (*) Unité de Neurobiologie Intégrative du Système Cholinergique, URA CNRS 2182, Institut Pasteur, Département de Neuroscience, 25 rue du Dr. Roux, 75015 Paris, France e-mail: granon@pasteur.fr A. Amadon : E. Giacomini : D. Le Bihan Service Hospitalier Frédéric Joliot, 4 place du général Leclerc, 91400 Orsay, France A. Wiklund Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden