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.

Findings: 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.

Figure 1

Adolescent locomotion following nicotine administration. Nicotine (0.5 mg/kg) was administered for 5 consecutive days to a/a mice (a), and A^vy/a mice (b). Data are presented as mean distance traveled in meters ± SE; n = 6–8 per group.

Figure 2

Young adult locomotion following nicotine administration. Nicotine (0.5 mg/kg) was administered for 5 consecutive days to a/a mice (a), and A^vy/a mice (b). Data are presented as mean distance traveled in meters ± SE; n = 5–8 per group. * p < .05, ** p < 0.01 significantly different from saline-matched controls.

Figure 3

Thigmotaxis in young adult mice following nicotine administration. Nicotine (0.5 mg/kg) was administered for 5 consecutive days to a/a mice (a), and A^vy/a mice (b). For graphical presentation, thigmotaxis was calculated as $1-\frac{\mathit{\text{distance}}\mathit{\text{traveled}}\mathit{\text{outside}}\mathit{\text{center}}\mathit{\text{of}}\mathit{\text{apparatus}}}{\mathit{\text{total}}\mathit{\text{distance}}\mathit{\text{traveled}}}$. Data are presented as mean ± SE; n = 5–8 per group. * p < 0.05 significantly different from saline-matched controls.

Figure 4

Serum corticosterone following nicotine (0.5 mg/kg) administration in young adult A^vy/a and a/a mice.n = 6–7 per group. *p < 0.05, ** p < 0.01 significantly different from saline-matched controls of the same genotype.