Department of Psychology, University of Kentucky, Lexington, KY 40536-0509, USA.
Psychopharmacology (Berl). 2009 Dec;207(3):391-400. doi: 10.1007/s00213-009-1667-4. Epub 2009 Sep 26.
d-Amphetamine (AMPH) is a widely prescribed attention deficit hyperactivity disorder medication, but little is known about its effects on impulsive choice with escalated use.
The current study examined the effects of short and long access to AMPH self-administration on impulsive choice in a delay discounting task in which rats chose between a small immediate reward (one sucrose pellet immediately) and a larger delayed reward (three sucrose pellets after an adjusting delay).
Following choice stability in delay discounting, all rats received 15 1-h sessions of AMPH self-administration (0.1 or 0.03 mg/kg/infusion); self-administration sessions began 45 min after each delay discounting session. Rats were then either maintained on the short access (ShA) self-administration session or were switched to a long access (LgA) 6-h session for 21 days, followed by a 7-day withdrawal phase in which only the delay discounting task continued.
LgA rats in the 0.03 mg/kg/infusion dose group escalated in total number of infusions across sessions, although rats in the 0.1 mg/kg/infusion dose group did not. LgA groups at both unit doses showed decreased mean adjusted delays across sessions compared to the ShA groups, indicating that long access to AMPH increases impulsive choice. During the AMPH withdrawal phase, LgA groups returned back to baseline mean adjusted delays, indicating that the effect on impulsive choice was reversible.
These results show that extended AMPH self-administration produces a transient loss of inhibitory control, which may play a role in the escalating pattern of drug intake that characterizes the addiction process.
右旋苯丙胺(AMPH)是一种广泛用于治疗注意力缺陷多动障碍的处方药物,但对于其在逐渐增加使用剂量时对冲动选择的影响知之甚少。
本研究在延迟折扣任务中检查了短时间和长时间接触 AMPH 自我给药对冲动选择的影响,其中大鼠在小的即时奖励(立即一个蔗糖丸)和大的延迟奖励(调整延迟后三个蔗糖丸)之间进行选择。
在延迟折扣稳定后,所有大鼠接受了 15 次 1 小时的 AMPH 自我给药(0.1 或 0.03 mg/kg/剂量);自我给药开始于每次延迟折扣后的 45 分钟。然后,大鼠要么继续进行短时间访问(ShA)自我给药,要么切换到 6 小时的长时间访问(LgA),持续 21 天,然后在 7 天的戒断期内仅继续进行延迟折扣任务。
在 0.03 mg/kg/剂量组中,LgA 组的总剂量在各次给药中逐渐增加,而在 0.1 mg/kg/剂量组中,大鼠则没有。两种单位剂量的 LgA 组的平均调整延迟在各次给药中均低于 ShA 组,表明长时间接触 AMPH 增加了冲动选择。在 AMPH 戒断期间,LgA 组恢复到基线平均调整延迟,表明冲动选择的影响是可逆的。
这些结果表明,延长的 AMPH 自我给药会导致短暂的抑制控制丧失,这可能在成瘾过程中特征性的药物摄入逐渐增加的模式中起作用。