title: Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits.
abstract: BACKGROUND
  Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms.
  
  
  METHODS
  Adolescent or adult male Sprague-Dawley rats received either nicotine water (10-75 μg/mL) or tap water for several weeks. Methamphetamine (4 × 7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day.
  
  
  RESULTS
  Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats.
  
  
  CONCLUSIONS
  Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which novel object recognition deficits are attenuated by nicotine in methamphetamine-treated rats.
authors.affiliation: Department of Pharmacology and Toxicology (Dr Vieira-Brock, Dr McFadden, Ms Nielsen, Dr Smith, Dr Hanson, and Dr Fleckenstein), and School of Dentistry (Drs Smith, Hanson, and Fleckenstein), University of Utah, Salt Lake City, UT.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Vieira-Brock
authors.affiliation: Department of Pharmacology and Toxicology (Dr Vieira-Brock, Dr McFadden, Ms Nielsen, Dr Smith, Dr Hanson, and Dr Fleckenstein), and School of Dentistry (Drs Smith, Hanson, and Fleckenstein), University of Utah, Salt Lake City, UT.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McFadden
authors.affiliation: Department of Pharmacology and Toxicology (Dr Vieira-Brock, Dr McFadden, Ms Nielsen, Dr Smith, Dr Hanson, and Dr Fleckenstein), and School of Dentistry (Drs Smith, Hanson, and Fleckenstein), University of Utah, Salt Lake City, UT.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Nielsen
authors.affiliation: Department of Pharmacology and Toxicology (Dr Vieira-Brock, Dr McFadden, Ms Nielsen, Dr Smith, Dr Hanson, and Dr Fleckenstein), and School of Dentistry (Drs Smith, Hanson, and Fleckenstein), University of Utah, Salt Lake City, UT.
authors.forename: Misty D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Department of Pharmacology and Toxicology (Dr Vieira-Brock, Dr McFadden, Ms Nielsen, Dr Smith, Dr Hanson, and Dr Fleckenstein), and School of Dentistry (Drs Smith, Hanson, and Fleckenstein), University of Utah, Salt Lake City, UT.
authors.forename: Glen R
authors.initials: GR
authors.lastname: Hanson
authors.affiliation: Department of Pharmacology and Toxicology (Dr Vieira-Brock, Dr McFadden, Ms Nielsen, Dr Smith, Dr Hanson, and Dr Fleckenstein), and School of Dentistry (Drs Smith, Hanson, and Fleckenstein), University of Utah, Salt Lake City, UT. annette.fleckenstein@hsc.utah.edu.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Fleckenstein
mesh_terms: D000284:Administration, Oral; D000375:Aging / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D060766:Drinking Water; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008694:Methamphetamine / Q000633:toxicity*; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage; D018697:Nootropic Agents / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013702:Temporal Lobe / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000473:pathology
chemical_list: D060766:Drinking Water; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; C403531:nicotinic receptor alpha4beta2; D008694:Methamphetamine; D009538:Nicotine
keywords: Methamphetamine; nicotine; nicotinic receptors; novel object recognition memory; serotonin transporter