Maguire D R, Henson C, France C P
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Br J Pharmacol. 2016 Apr;173(8):1350-62. doi: 10.1111/bph.13434. Epub 2016 Feb 26.
Repeated administration of a μ opioid receptor agonist can enhance some forms of impulsivity, such as delay discounting. However, it is unclear whether repeated administration alters motor impulsivity.
We examined the effects of acute administration of morphine and amphetamine prior to and during daily morphine administration in rats responding under a five-choice serial reaction time task. Rats (n = 5) were trained to detect a brief flash of light presented randomly in one of five response holes; responding in the target hole delivered food, whereas responding in the wrong hole or responding prior to illumination of the target stimulus (premature response) initiated a timeout. Premature responding served as an index of motor impulsivity.
Administered acutely, morphine (0.1-10 mg·kg(-1) , i.p.) increased omissions and modestly, although not significantly, premature responding without affecting response accuracy; amphetamine (0.1-1.78 mg·kg(-1) , i.p.) increased premature responding without changing omissions or response accuracy. After 3 weeks of 10 mg·kg(-1) ·day(-1) morphine, tolerance developed to its effects on omissions whereas premature responding increased approximately fourfold, compared with baseline. Effects of amphetamine were not significantly affected by daily morphine administration.
These data suggest that repeated administration of morphine increased effects of morphine on motor impulsivity, although tolerance developed to other effects, such as omissions. To the extent that impulsivity is a risk factor for drug abuse, repeated administration of μ opioid receptor agonists, for recreational or therapeutic purposes, might increase impulsivity and thus the risk for drug abuse.
反复给予μ阿片受体激动剂可增强某些形式的冲动性，如延迟折扣。然而，反复给药是否会改变运动冲动性尚不清楚。
我们在大鼠进行五选择连续反应时任务的过程中，研究了在每日给予吗啡之前和期间急性给予吗啡和苯丙胺的效果。将大鼠（n = 5）训练以检测随机出现在五个反应孔之一中的短暂闪光；在目标孔中做出反应可获得食物，而在错误的孔中做出反应或在目标刺激亮起之前做出反应（过早反应）会引发超时。过早反应作为运动冲动性的指标。
急性给予吗啡（0.1 - 10 mg·kg⁻¹，腹腔注射）会增加遗漏次数，并适度增加过早反应，但不显著，且不影响反应准确性；苯丙胺（0.1 - 1.78 mg·kg⁻¹，腹腔注射）增加过早反应，但不改变遗漏次数或反应准确性。在给予10 mg·kg⁻¹·天⁻¹吗啡3周后，对其对遗漏次数的影响产生了耐受性，而过早反应与基线相比增加了约四倍。每日给予吗啡对苯丙胺的作用没有显著影响。
这些数据表明，反复给予吗啡会增加吗啡对运动冲动性的影响，尽管对其他影响（如遗漏次数）产生了耐受性。就冲动性是药物滥用的危险因素而言，出于娱乐或治疗目的反复给予μ阿片受体激动剂可能会增加冲动性，从而增加药物滥用的风险。
