Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Behav Brain Res. 2023 Sep 13;453:114612. doi: 10.1016/j.bbr.2023.114612. Epub 2023 Aug 4.
Reward uncertainty can sensitize reward pathways, promoting increased reward-seeking and -taking behaviours. This is relevant to human conditions such as pathological gambling, eating disorders and drug addiction. In the context of addiction, preclinical self-administration procedures have been developed to model the intermittency of human drug use. These intermittent-access (IntA) procedures involve intermittent but predictable access to drug during self-administration sessions. However, human drug use typically involves intermittent and unpredictable drug access. We introduce a new procedure modeling unpredictable, intermittent access (UIntA) to a reinforcer, and we compare it to procedures that provide predictable reinforcer availability; continuous (ContA) or intermittent (IntA) access. Female rats self-administered water or liquid sucrose in daily hour-long sessions. IntA and ContA rats had access to a fixed volume of water or sucrose (0.1 ml), under a fixed ratio 3 schedule of reinforcement. IntA rats had predictable 5-min reinforcer ON and 25-min reinforcer OFF periods. ContA rats had 60 min of reinforcer access during each session. For UIntA rats, variation in the length of ON and OFF periods (1, 5 or 9 min/period), response requirement (variable ratio 3 schedule of reinforcement), reinforcer probability (50%) and quantity (0, 0.1 or 0.2 ml) introduced reward uncertainty. Following 14 daily self-administration sessions, UIntA rats showed the highest levels of responding for water or sucrose under progressive ratio conditions, responding under extinction conditions, and cue-induced reinstatement of sucrose seeking. Thus, unpredictable, intermittent reward access promotes increased reward pursuit. This has implications for modeling addiction and other disorders of increased reward seeking.
奖励不确定性可以使奖励途径敏感化,促进增加的奖励寻求和采取行为。这与病理性赌博、饮食失调和药物成瘾等人类状况有关。在成瘾的背景下,已经开发了临床前自我给药程序来模拟人类药物使用的间歇性。这些间歇性访问(IntA)程序涉及在自我给药会议期间间歇性但可预测地获得药物。然而,人类药物使用通常涉及不可预测的间歇性药物获取。我们引入了一种新的程序来模拟不可预测的间歇性奖励获取(UIntA),并将其与提供可预测奖励可用性的程序进行比较;连续(ContA)或间歇性(IntA)访问。雌性大鼠在每天一小时的长会议中自我给予水或液体蔗糖。IntA 和 ContA 大鼠可以根据固定比例 3 的强化时间表获得固定体积的水或蔗糖(0.1 ml)。IntA 大鼠有可预测的 5 分钟奖励 ON 和 25 分钟奖励 OFF 期。ContA 大鼠在每次会议中都有 60 分钟的奖励时间。对于 UIntA 大鼠,ON 和 OFF 期的长度变化(1、5 或 9 分钟/期)、反应要求(可变比例 3 的强化时间表)、奖励概率(50%)和数量(0、0.1 或 0.2 ml)引入了奖励不确定性。在 14 天的每日自我给药会议后,UIntA 大鼠在递增比率条件下对水或蔗糖表现出最高水平的反应,在消退条件下表现出反应,以及对蔗糖寻求的线索诱导再巩固。因此,不可预测的间歇性奖励获取促进了更多的奖励追求。这对建模成瘾和其他增加奖励寻求的障碍有影响。