Kappa opioid receptor mediated operant performance in male and female rats

IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES
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Abstract

Anhedonia and avolition are emotions frequently endorsed by individuals with stress related disorders. Kappa opioid receptor (KOR) activation can induce negative emotions and recent clinical evidence suggests that KOR antagonism can alleviate anhedonia in a transdiagnostic cohort of patients. However, the behavioral consequences of KOR activation and antagonism in modulating motivation, as assessed by schedule-controlled behavioral performance without preexisting conditions (stress or substance use), have not been formally assessed. To address this gap in the literature, this report utilized male and female Sprague Dawley rats to (1) evaluate the impact of the selective KOR agonist U50,488, on the performance of animals responding for sucrose pellets under a progressive ratio (PR) schedule and (2) determine the effects of the short-acting KOR antagonist LY2444296 alone and on U50,488 mediated reductions in PR performance. Overall, U50,488 5 mg/kg significantly reduced the breakpoint and number of rewards obtained by animals. This occurred in the absence of motor impairment and independent of evidence for satiation. LY2444296 did not alter PR performance when administered alone but effectively blocked the deficits induced by U50,488. To further delineate the behavioral alterations that underlie these reductions in responding, a more detailed analysis was conducted on PR performance in the first 15 min of the session, the period of time when animals obtained the most reinforcers. During this period, U50,488 increased the length of the post-reinforcement pause and reduced the running rate on PR schedules. These changes in behavior produced by acute activation of KORs are consistent with a reduction of effort-related motivation in rodents. These data contribute to the understanding of how KORs modulate motivation, which is critical to future efforts to evaluate performance in the context of stress and assess how KOR antagonists alleviate anhedonic behaviors associated with stress.

雌雄大鼠的 Kappa 阿片受体介导的操作表现。
失乐症和逃避是压力相关障碍患者经常表现出的情绪。卡巴阿片受体(KOR)激活可诱发消极情绪,最近的临床证据表明,KOR拮抗剂可缓解跨诊断群患者的失乐症。然而,KOR激活和拮抗在调节动机方面的行为后果尚未得到正式评估,这种行为后果是在没有预先存在的条件(压力或药物使用)的情况下,通过日程表控制的行为表现来评估的。为了填补这一文献空白,本报告利用雄性和雌性 Sprague Dawley 大鼠(1)评估选择性 KOR 激动剂 U50,488 对动物在累进比率(PR)计划下对蔗糖颗粒做出反应的表现的影响;(2)确定短效 KOR 拮抗剂 LY2444296 单独使用以及对 U50,488 介导的 PR 表现下降的影响。总体而言,U50,488 5 毫克/千克可显著降低动物的断点和获得奖励的次数。这发生在没有运动损伤的情况下,与饱食证据无关。单独施用 LY2444296 不会改变动物的 PR 表现,但能有效阻止 U50,488 诱导的缺陷。为了进一步确定导致这些反应减少的行为改变,我们对动物在获得最多强化物的前 15 分钟内的 PR 表现进行了更详细的分析。在此期间,U50,488 增加了强化后暂停的时间,并降低了 PR 计划的运行率。急性激活 KORs 所产生的这些行为变化与啮齿动物努力相关动机的降低是一致的。这些数据有助于人们了解 KORs 如何调节动机,这对于今后评估压力下的表现以及评估 KOR 拮抗剂如何减轻与压力相关的厌食行为至关重要。
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来源期刊
CiteScore
6.40
自引率
2.80%
发文量
122
审稿时长
38 days
期刊介绍: Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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