title: Age-specific locomotor response to nicotine in yellow and mottled yellow A(vy)/a mice.
abstract: BACKGROUND
  Most Agouti viable yellow (Avy) mice display constitutive expression of agouti protein, which acts as an inverse agonist at the melanocortin receptor 4 (Mc4r), resulting in adult-onset obesity as well as an altered sensitivity to some drugs of abuse. We investigated the influence of excessive agouti expression on open-field locomotor response to daily 0.5 mg/kg (-)-freebase nicotine injections in 27 early adolescent and 27 young adult male Avy/a and a/a mice, and assessed the effects of nicotine administration (0.5 mg/kg) followed by open-field testing on serum corticosterone levels in a separate group of 25 young adult male Avy/a and a/a mice.
  
  
  RESULTS
  Young adult Avy/a mice displayed pronounced nicotine-induced hypolocomotion (a 24% reduction in distance traveled) compared to their a/a littermates. Early adolescent Avy/a mice did not differ from their a/a littermates or saline-matched controls in locomotion following nicotine administration. Young adult Avy/a mice also displayed increased thigmotaxis (a 5% increase in time spent outside the center of the apparatus) on the first day of nicotine administration as compared to saline-matched controls, while a/a mice did not. An increase in serum corticosterone levels 20 minutes after nicotine injection in a separate group of young adult male mice (n = 25) was proportionally similar between Avy/a and a/a mice.
  
  
  CONCLUSIONS
  Overall, the results suggest an age- and epigenotype- or genotype-specific response to nicotine administration in young adult male Avy/a mice. It appears the Avy/a locomotor and thigmotaxic responses to acute nicotine administration are not mediated solely by hypothalamic-pituitary-adrenal (HPA) axis stimulation.
authors.affiliation: Department of Biobehavioral Health, The Pennsylvania State University, 219 Biobehavioral Health Building, 16802 University Park, PA, USA. djv4@psu.edu.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Dingman
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Gyekis
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Whetzel
authors.forename: Laura Cousino
authors.initials: LC
authors.lastname: Klein
authors.forename: David J
authors.initials: DJ
authors.lastname: Vandenbergh
mesh_terms: D000367:Age Factors; D000818:Animals; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*
chemical_list: D009538:Nicotine