title: Stimulation of nicotine reward and central cholinergic activity in Sprague-Dawley rats exposed perinatally to a fat-rich diet.
abstract: BACKGROUND
  While clinical studies show maternal consumption of palatable fat-rich diets during pregnancy to negatively impact the children's behaviors and increase their vulnerability to drug abuse, the precise behavioral and neurochemical mechanisms mediating these phenomena have yet to be examined.
  
  
  OBJECTIVE
  The study examined in rats whether gestational exposure to a high-fat diet (HFD) can increase the offspring's propensity to use nicotine and whether disturbances in central nicotinic cholinergic signaling accompany this behavioral effect.
  
  
  METHODS
  Rat offspring exposed perinatally to a HFD or chow diet were characterized in terms of their nicotine self-administration behavior in a series of operant response experiments and the activity of acetylcholinesterase (AChE) and density of nicotinic ACh receptors (nAChRs) in different brain areas.
  
  
  RESULTS
  Perinatal HFD compared to chow exposure increased nicotine-self administration behavior during fixed ratio and dose-response testing and caused an increase in breakpoint using progressive ratio testing, while nicotine seeking in response to nicotine prime-induced reinstatement was reduced. This behavioral change induced by the HFD was associated with a significant reduction in activity of AChE in the midbrain, hypothalamus, and striatum and increased density of β2-nAChRs in the ventral tegmental area and substantia nigra and of α7-nAChRs in the lateral and ventromedial hypothalamus.
  
  
  CONCLUSIONS
  Perinatal exposure to a HFD increases the vulnerability of the offspring to excessive nicotine use by enhancing its reward potential, and these behavioral changes are accompanied by a stimulation of nicotinic cholinergic signaling in mesostriatal and hypothalamic brain areas important for reinforcement and consummatory behavior.
authors.affiliation: Laboratory of Behavioral Neurobiology, Rockefeller University, New York, NY, 10065, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Morganstern
authors.forename: Olga
authors.initials: O
authors.lastname: Lukatskaya
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Moon
authors.forename: Wei-Ran
authors.initials: WR
authors.lastname: Guo
authors.forename: Jane
authors.initials: J
authors.lastname: Shaji
authors.forename: Olga
authors.initials: O
authors.lastname: Karatayev
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Leibowitz
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology; D059305:Diet, High-Fat; D005260:Female; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D015398:Signal Transduction / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D000110:Acetylcholinesterase; D009538:Nicotine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor