■一线抗抑郁药,如选择性5-羟色胺再摄取抑制剂(SSRIs),使许多患者的治疗需求得不到满足。此外,即使SSRIs减轻了抑郁症状,快感缺失,对以前有回报的活动失去乐趣,经常不减。这种状况令人沮丧,并要求开发更直接治疗快感缺乏症的药物。非典型迷幻药3,4-亚甲二氧基甲基苯丙胺(MDMA)可能有希望作为一种促性腺激药,因为它可以有效地用于治疗抗性的创伤后应激障碍和共病抑郁症。然而,除了它作为entactogen的亲社会效应之外,MDMA也与神经毒性认知缺陷有关。本研究旨在检查MDMA在三个不同行为领域中在雌性和雄性大鼠中的相对效力,以帮助定义MDMA的临床前概况作为候选的前激素治疗。
■首先,使用触摸屏概率奖励任务(PRT)检查奖励响应度的信号检测指标,用于客观量化人类无张力表型的反向翻译测定法。第二,为了探究潜在的认知缺陷,使用基于触摸屏的精神运动警惕性和延迟位置匹配测定法来检查注意力过程和短期空间记忆,分别。最后,通过机器学习分析促进的社会互动成对评估,研究了MDMA的内生效应。
■研究结果表明(1)由PRT量化的奖励响应率的剂量依赖性增加,(2)注意和短期记忆的剂量依赖性缺陷,(3)男性而非女性受试者的亲社会互动方面的剂量依赖性增加。MDMA的理想(促性腺激)或不良(认知破坏)作用均未持续超过24小时。
■目前的结果将MDMA描述为一种有前途的前调质治疗,尽管急性给药后短期认知障碍有一定的责任。
UNASSIGNED: Frontline antidepressants such as selective serotonin reuptake inhibitors (SSRIs) leave many patients with unmet treatment needs. Moreover, even when SSRIs reduce depressive symptoms, anhedonia, the loss of pleasure to previously rewarding activities, often remains unabated. This state of affairs is disheartening and calls for the development of medications to more directly treat anhedonia. The atypical psychedelic 3,4-methylenedioxymethamphetamine (MDMA) might have promise as a prohedonic medication given its efficacious applications for treatment-resistant post-traumatic stress disorder and comorbid depression. However, in addition to its prosocial effects as an entactogen, MDMA is also associated with neurotoxic cognitive deficits. The present studies were designed to examine the relative potency of MDMA in female and male rats across three distinct behavioral domains to assist in defining a preclinical profile of MDMA as a candidate prohedonic therapeutic.
UNASSIGNED: First, signal detection metrics of reward responsivity were examined using the touchscreen probabilistic reward task (PRT), a reverse-translated assay used to objectively quantify anhedonic phenotypes in humans. Second, to probe potential cognitive deficits, touchscreen-based assays of psychomotor vigilance and delayed matching-to-position were used to examine attentional processes and short-term spatial memory, respectively. Finally, MDMA\'s entactogenic effects were studied via pairwise assessments of social interaction facilitated by machine-learning analyses.
UNASSIGNED: Findings show (1) dose-dependent increases in reward responsivity as quantified by the PRT, (2) dose-dependent deficits in attention and short-term memory, and (3) dose-dependent increases in aspects of prosocial interaction in male but not female subjects. Neither the desirable (prohedonic) nor undesirable (cognition disruptive) effects of MDMA persisted beyond 24 h.
UNASSIGNED: The present results characterize MDMA as a promising prohedonic treatment, notwithstanding some liability for short-lived cognitive impairment following acute administration.