Baseline-dependency: How genotype and signaled delays influence amphetamine's effects on delay discounting

Abstract

Rationale: Delay discounting, in which an animal chooses between a small, immediate or large, delayed reinforcer, is an experimental model of impulsivity. In previous studies, d-amphetamine has both increased and decreased preference for larger-delayed reinforcers depending on experimental conditions.

Objective: Identify genotype X environment interactions responsible for these disparate findings in a single study and assess the hypothesis that baseline-dependence unifies d-amphetamine's effects.

Methods: Delay discounting by BALB/c and C57Bl/6 mice was evaluated using a choice procedure in which six delays to a larger reinforcer were presented in a single session. Components were presented both with and without stimuli that uniquely signaled reinforcer delays. d-Amphetamine's (0.1-1.7 mg/kg) effects on delay and magnitude sensitivity were assessed when specific stimuli did or did not uniquely signal the delay to a larger reinforcer. d-Amphetamine's effects were determined using a model-comparison approach.

Results: During baseline, magnitude and delay sensitivity were identical across signal conditions for BALB/c mice and generally greater than the C57Bl/6 mice. For C57Bl/6 mice, magnitude and delay sensitivity were higher during the signaled than the unsignaled component. Amphetamine decreased delay sensitivity during both components for BALB/c mice, but this effect was attenuated by delay-specific stimuli. For C57Bl/6 mice, amphetamine decreased their high magnitude and delay sensitivity when delays were signaled and, conversely, increased the low magnitude and delay sensitivity when delays were unsignaled.

Conclusions: BALB/c mice showed high delay and magnitude sensitivity regardless of signal conditions. C57Bl/6's magnitude and delay sensitivity depended on signaling. d-Amphetamine usually decreased high baseline delay- and magnitude sensitivity and increased low sensitivities, a baseline-dependence that occurred regardless of whether delay sensitivity was driven by biological (genotype) or environmental (signaling) variables. The C57Bl/6 mouse may be a good model of environmentally-induced impulsivity while BALB/c mice could model impulsivity with a strong genetic contribution.

Keywords: Amphetamine; Baseline dependency; Delay discounting; Model comparison; Mouse strain; Signaled delays.