Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA.
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Psychopharmacology (Berl). 2018 Aug;235(8):2447-2457. doi: 10.1007/s00213-018-4943-3. Epub 2018 Jun 16.
The synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone.
The binge-like acquisition pattern is novel for rat IVSA; thus, the present study sought to determine if this effect generalizes to IVSA of α-PVP in female rats.
Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers containing an activity wheel. Groups were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move.
Approximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution.
This confirms the high reinforcer effectiveness of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.
合成卡西酮 α-吡咯戊基苯丙胺(α-PVP)与使用者的奇特公众行为有关。这种行为与药物使用的长时间狂欢有关,这促使人们进行了更多的研究,特别是因为先前的一项研究发现,一半的雄性大鼠经历了一次异常高摄入量的狂欢,随后在获得静脉内自我给药(IVSA)的相关药物 3,4-亚甲二氧基吡咯戊酮期间,自我给药的水平持续较低。
这种狂欢样的获取模式是大鼠 IVSA 的新发现;因此,本研究旨在确定这种效应是否适用于雌性大鼠的 α-PVP 的 IVSA。
雌性 Wistar 大鼠在含有活动轮的 IVSA 实验室内接受 α-PVP(0.05mg/kg/inf)的训练。实验组大鼠的活动轮固定(无轮组),或在获得的前 5 天固定,或在整个获得期间自由移动(轮组)。然后,这些组被置于轮访问开关下,然后所有动物都接受剂量替代(0.0125-0.3mg/kg/inf),活动轮交替固定和自由移动。
大约一半的大鼠在 IVSA 模式开始时出现了一天异常高的药物摄入量狂欢,与轮访问条件无关。在获得后的轮访问开关中,无轮组的轮活动明显较低。轮访问训练组的剂量效应曲线相似,对于狂欢/非狂欢表型亚组也是如此,并且在剂量替代期间,轮访问并没有改变。
这证实了 α-PVP 在雌性大鼠中的高强化效力,以及伴随的轮活动作为自然奖励的贬值。