Differential effects of d-amphetamine and atomoxetine on risk-based decision making of Lewis and Fischer 344 rats

Abstract

Individuals with attention-deficit/hyperactivity disorder tend to make risker choices during probabilistic-discounting procedures. Thus, how common attention-deficit/hyperactivity disorder medications affect probabilistic discounting is of interest. In general, d-amphetamine increases risk-taking while atomoxetine has produced mixed effects in rats. Results from previous studies may result from genetic factors. Lewis and F344 rats have neurochemical differences that may be relevant to probabilistic discounting and how drugs affect such behavior. In this study, we evaluated dose-dependent effects of d-amphetamine and atomoxetine on probabilistic discounting of Lewis and F344. Male Lewis and F344 chose between one food pellet delivered 100% of the time and three food pellets delivered following decreasing probabilities of delivery (i.e. 100%, 66.7%, 33.3%, 16.5%, and 8.25%). Saline, d-amphetamine (0.1-1.8 mg/kg), and atomoxetine (0.1-7.8 mg/kg) were tested acutely. Lewis and F344 did not differ in choice at baseline. d-Amphetamine increased risky choice for both rat strains at low-to-moderate doses, although it did so at a lower dose (0.1 and 0.3 mg/kg) for F344 as compared to Lewis (0.3 mg/kg only). At high doses (1.0 and 1.8 mg/kg), d-amphetamine disrupted choice, increased frequencies of omitted trials, and reduced reinforcer sensitivity. Although atomoxetine increased frequencies of omitted trials at high doses (5.6 and 7.8 mg/kg), it had no effect on probabilistic discounting for either rat strain. Although Lewis and F344 differ in various types of impulsivity (i.e. motor, choice), with Lewis being the more impulsive of the two, the present results suggest that Lewis and F344 do not differ in risk-based decision-making. Effects of d-amphetamine on probabilistic discounting may be biology-dependent and differ from effects of atomoxetine.

Fig. 1

(Left) Percent larger-reinforcer choice as a function of decreasing probabilities of larger-reinforcer delivery for LEW (filled squares) and F344 (unfilled squares) at baseline. (Right) Win-stay and lose-shift ratios for LEW (filled bars) and F344 (unfilled bars) at baseline. Error bars represent SEM. Asterisks represent a statistically significant difference between rat strains (P < 0.05). LEW, Lewis.

Fig. 2

Percent larger-reinforcer choice as a function of decreasing probabilities of larger-reinforcer delivery for LEW (left panel) and F344 (right panel) across all doses of acute d-AMP. Error bars represent SEM. Asterisks represent a statistically significant difference from saline vehicle at that block (P’s < 0.05). Note that sample sizes for higher doses of d-AMP are provided in parenthesis in the figure legends given that data for some rats were excluded at these doses due to omitted trials. LEW, Lewis; SAL, saline vehicle.

Fig. 3

Win-stay (left panel) and lose-shift (right panel) ratios for LEW (filled bars) and F344 (unfilled bars) across all doses of acute d-AMP. Error bars represent SEM. Asterisks represent a statistically significant difference from saline vehicle (P’s < 0.05). Note that for 1.0 mg/kg, n = 7 F344 and for 1.8 mg/kg, n = 7 LEW and n = 3 F344 given that data for some rats were excluded at these doses due to omitted trials. There may be something wrong with this figure–text and stars!!–Ed. But maybe this is a quirk of Word–it looks OK in the pdf. C, control (no-drug) sessions; d-AMP, d-amphetamine; LEW, Lewis; S, saline vehicle.

Fig 4

Percent larger-reinforcer choice as a function of decreasing probabilities of larger-reinforcer delivery for LEW (left panel) and F344 (right panel) across all doses of acute ATO. Error bars represent SEM. LEW, Lewis; SAL, saline vehicle.

Fig 5

Win-stay (left panel) and lose-shift (right panel) ratios for LEW (filled bars) and F344 (unfilled bars) across all doses of acute ATO. C, control (no-drug) sessions; LEW, Lewis; S, saline vehicle. Error bars represent SEM.