Fox Foundation, 4848 W. Gandy Blvd, Tampa, FL 33611, United States of America.
Rawl 222, Mail Stop 565, East Carolina University, Greenville, NC 27858-4353, United States of America.
Pharmacol Biochem Behav. 2020 Dec;199:173070. doi: 10.1016/j.pbb.2020.173070. Epub 2020 Nov 2.
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.
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.
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.
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.
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.
延迟折扣是指动物在小而即时的奖励与大而延迟的奖励之间做出选择，这是一种冲动性的实验模型。在之前的研究中，根据实验条件，安非他命既能增加也能减少对大延迟奖励的偏好。
在一项单一的研究中确定导致这些不同发现的基因型与环境的相互作用，并评估一个假设，即基线依赖性将安非他命的作用统一起来。
使用选择程序评估 BALB/c 和 C57Bl/6 小鼠的延迟折扣，其中在一个单一的会议中呈现六个更大的奖励的延迟。在有和没有独特地标记奖励延迟的刺激的情况下呈现成分。当特定的刺激确实或确实没有独特地标记更大的奖励的延迟时，评估安非他命（0.1-1.7mg/kg）对延迟和幅度敏感性的影响。使用模型比较方法确定安非他命的作用。
在基线时，信号条件对 BALB/c 小鼠的幅度和延迟敏感性是相同的，并且通常大于 C57Bl/6 小鼠。对于 C57Bl/6 小鼠，在有信号的成分中幅度和延迟敏感性高于无信号的成分。安非他命降低了 BALB/c 小鼠在两个成分中的延迟敏感性，但这种作用被延迟特异性刺激所减弱。对于 C57Bl/6 小鼠，当延迟被信号标记时，安非他命降低了它们的高幅度和延迟敏感性，相反，当延迟未被信号标记时，增加了低幅度和延迟敏感性。
BALB/c 小鼠无论信号条件如何，都表现出高的延迟和幅度敏感性。C57Bl/6 的幅度和延迟敏感性取决于信号。安非他命通常降低高基线延迟和幅度敏感性，并增加低敏感性，这种基线依赖性发生在延迟敏感性是由生物（基因型）还是环境（信号）变量驱动的情况下。C57Bl/6 小鼠可能是环境诱导冲动性的良好模型，而 BALB/c 小鼠可能具有强烈遗传贡献的冲动性模型。
