Floresco Stan B, Whelan Jennifer M
Department of Psychology and Brain Research Center, University of British Columbia, 2136 West Mall, Vancouver, BC V6T1Z4, Canada.
Psychopharmacology (Berl). 2009 Aug;205(2):189-201. doi: 10.1007/s00213-009-1529-0. Epub 2009 Apr 14.
Psychostimulant abuse has been linked to impairments in cost-benefit decision making.
We assessed the effects of repeated amphetamine (AMPH) treatment in rodents on two distinct forms of decision making.
Separate groups of rats were trained for 26 days on either a probabilistic (risk) or effort-discounting task, each consisting of four discrete blocks of ten choice trials. One lever always delivered a smaller reward (one or two pellets), whereas another lever delivered a four-pellet reward. For risk-discounting, the probability of receiving the larger reward decreased across trial blocks (100-12.5%), whereas on the effort task, four pellets could be obtained after a ratio of presses that increased across blocks (2-20). After training, rats received 15 saline or AMPH injections (escalating from 1 to 5 mg/kg) and were then retested during acute and long-term withdrawal.
Repeated AMPH administration increased risky choice 2-3 weeks after drug exposure, whereas these treatments did not alter effort-based decision making in a separate group of animals. However, prior AMPH exposure sensitized the effects of acute AMPH on both forms of decision making, whereby lower doses were effective at inducing "risky" and "lazy" patterns of choice.
Repeated AMPH exposure leads to relatively long-lasting increases in risky choice, as well as sensitization to the effects of acute AMPH on different forms of cost/benefit decision making. These findings suggest that maladaptive decision-making processes exhibited by psychostimulant abusers may be caused in part by repeated drug exposure.
精神兴奋剂滥用与成本效益决策受损有关。
我们评估了在啮齿动物中重复给予苯丙胺(AMPH)对两种不同决策形式的影响。
将单独的大鼠组在概率(风险)或努力折扣任务上训练26天,每个任务由四个包含十次选择试验的离散块组成。一个杠杆总是提供较小的奖励(一或两颗食丸),而另一个杠杆提供四颗食丸的奖励。对于风险折扣,获得较大奖励的概率在各试验块中逐渐降低(100%-12.5%),而在努力任务中,在各块中逐渐增加的按压次数比例后可获得四颗食丸(2-20)。训练后,大鼠接受15次生理盐水或AMPH注射(剂量从1毫克/千克递增至5毫克/千克),然后在急性和长期戒断期间进行重新测试。
重复给予AMPH在药物暴露后2至3周增加了风险选择,而这些处理并未改变另一组动物基于努力的决策。然而,先前的AMPH暴露使急性AMPH对两种决策形式的影响敏感化,即较低剂量有效地诱导了“风险”和“懒惰”的选择模式。
重复的AMPH暴露导致风险选择相对持久地增加,以及对急性AMPH对不同形式成本/效益决策影响的敏感化。这些发现表明,精神兴奋剂滥用者表现出的适应不良决策过程可能部分是由重复的药物暴露引起的。