Age-specific locomotor response to nicotine in yellow and mottled yellow A§ssup§vy§esup§/a mice

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