title: Acute nicotine administration increases BOLD fMRI signal in brain regions involved in reward signaling and compulsive drug intake in rats.
abstract: BACKGROUND
  Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine.
  
  
  METHODS
  Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03-0.6 mg/kg) on the BOLD signal was investigated for 10 min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated.
  
  
  RESULTS
  A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal.
  
  
  CONCLUSIONS
  These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function.
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng). awbruijn@ufl.edu.
authors.forename: Adrie W
authors.initials: AW
authors.lastname: Bruijnzeel
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Jon C
authors.initials: JC
authors.lastname: Alexander
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Perez
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Rayna
authors.initials: R
authors.lastname: Bauzo-Rodriguez
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Hall
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Rachel
authors.initials: R
authors.lastname: Klausner
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Valerie
authors.initials: V
authors.lastname: Guerra
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Huadong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Moe
authors.initials: M
authors.lastname: Igari
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL (Drs Bruijnzeel, Alexander, Perez, Bauzo-Rodriguez, Hall, Klausner, Guerra, Igari, and Febo); Advanced Magnetic Resonance Imaging and Spectroscopy Facility (AMRIS), University of Florida, Gainesville, FL (Dr Zeng).
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003192:Compulsive Behavior / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D008279:Magnetic Resonance Imaging; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D017208:Rats, Wistar; D012201:Reward
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D010100:Oxygen
keywords: addiction; compulsive behavior; nicotine; pharmacological fMRI; rats; reward.