Huskinson S L, Freeman K B, Petry N M, Rowlett J K
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA.
Program in Neuroscience, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA.
Psychopharmacology (Berl). 2017 Aug;234(15):2353-2364. doi: 10.1007/s00213-017-4659-9. Epub 2017 Jun 10.
The schedule of drug availability may enhance choice of a drug. In non-human subjects, reinforcers are chosen more often when available under variable schedules of reinforcement relative to fixed schedules.
To determine whether variable-drug access is an important determinant of cocaine choice by manipulating the schedule, drug dose, and combination of schedule + dose.
Four male rhesus monkeys chose between cocaine doses (0.025-0.4 mg/kg/injection). In control conditions, the schedule and dose of each drug delivery were fixed. In other conditions, the reinforcement schedule (i.e., variable-ratio schedule), dose of each cocaine delivery, or both were variable on one lever while all aspects on the other lever remained fixed.
When cocaine dose was equal on average (0.1 mg/kg/injection), 2 of 4 subjects chose cocaine associated with the variable schedule more than the fixed schedule. All subjects chose the variable dose that was equal on average to the fixed dose, and this difference was statistically significant. Three of 4 subjects chose cocaine associated with the variable combination over the fixed option (when the dose was equal on average). During dose-response determinations (when dose on the variable and fixed options were not equal), making the schedule, dose, or both variable generally did not alter cocaine's potency as a reinforcer.
While many factors contribute to drug choice, unpredictable drug access is a feature that may be common in the natural environment and could play a key role in the allocation of behavior to drug alternatives by patients with substance-use disorders.
药物可得性的模式可能会增加对某种药物的选择。在非人类受试者中,相对于固定模式,当强化物在可变强化模式下可得时,被选择的频率更高。
通过操纵模式、药物剂量以及模式+剂量的组合,来确定可变药物获取是否是可卡因选择的一个重要决定因素。
四只雄性恒河猴在不同可卡因剂量(0.025 - 0.4毫克/千克/注射)之间进行选择。在对照条件下,每次给药的模式和剂量是固定的。在其他条件下,一个杠杆上的强化模式(即可变比率模式)、每次可卡因给药的剂量或两者都是可变的,而另一个杠杆上的所有方面保持固定。
当可卡因平均剂量相等(0.1毫克/千克/注射)时,4只受试者中有2只选择与可变模式相关的可卡因多于固定模式。所有受试者都选择了平均与固定剂量相等的可变剂量,且这种差异具有统计学意义。4只受试者中有3只选择与可变组合相关的可卡因而非固定组合(当平均剂量相等时)。在剂量反应测定期间(当可变和固定选项上的剂量不相等时),使模式、剂量或两者可变通常不会改变可卡因作为强化物的效力。
虽然许多因素会影响药物选择,但不可预测的药物获取是自然环境中可能常见的一个特征,并且可能在物质使用障碍患者将行为分配到不同药物选择方面发挥关键作用。