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Background  Most  Agouti viable yellow  ( A   vy  ) 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  A   vy   /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  A   vy   /a  and  a/a  mice.    Findings  Young adult  A   vy   /a  mice displayed pronounced nicotine-induced hypolocomotion (a 24% reduction in distance traveled) compared to their  a/a  littermates. Early adolescent  A   vy   /a  mice did not differ from their  a/a  littermates or saline-matched controls in locomotion following nicotine administration. Young adult  A   vy   /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  A   vy   /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  A   vy   /a  mice. It appears the  A   vy   /a  locomotor and thigmotaxic responses to acute nicotine administration are not mediated solely by hypothalamic-pituitary-adrenal (HPA) axis stimulation.

Age-specific locomotor response to nicotine in yellow and mottled yellow Avy/a mice