Department of Psychology, Western Michigan University, Kalamazoo, Michigan, USA.
Behav Pharmacol. 2021 Sep 1;32(6):524-532. doi: 10.1097/FBP.0000000000000647.
3,4-Methylenedioxypyrovalerone (MDPV), one of several synthetic cathinones, is a popular constituent of illicit 'bath salts'. In preclinical studies utilizing drug discrimination methods with male rodents, MDPV has been characterized as similar to both cocaine and 3,4-methylenedioxymethamphetamine-hydrochloride (MDMA). Whereas few drug discrimination studies have utilized female rats, the current study evaluated the discriminative stimulus effects of MDPV in 12 adult female Sprague-Dawley rats trained to discriminate 0.5 mg/kg MDPV from saline under a fixed ratio 20 schedule of food reinforcement. Stimulus substitution was assessed with MDPV and its enantiomers, other synthetic cathinones [alpha pyrrolidinopentiophenone-hydrochloride(α-PVP), 4-methylmethcathinone (4-MMC)], other dopamine agonists (cocaine, [+)-methamphetamine] and serotonin agonists [MDMA, lysergic acid diethylamide (LSD)] Stimulus antagonism was assessed with the dopamine D1 receptor antagonist, Sch 23390 and the D2 receptor antagonist, haloperidol. Cocaine and (+)-methamphetamine engendered full stimulus generalization to MDPV with minimal effects on response rate. LSD produced partial substitution, whereas MDMA and 4-MMC produced complete substitution, and all these serotonergic compounds produced dose-dependent response suppression. (S)-MDPV and α-PVP engendered full substitution with similar potency to the racemate, while (R)-MDPV failed to substitute up to 5 mg/kg. Both Sch 23390 and haloperidol attenuated the discrimination of low MDPV doses and essentially shifted the dose-response curve to the right but failed to block discrimination of the training dose. These findings are generally consistent with previous reports based exclusively on male rodents. Moreover, they confirm the contribution of dopaminergic mechanisms but do not rule out the possible contribution of other neurotransmitter actions to the interoceptive stimulus effects of MDPV.
3,4-亚甲基二氧吡咯戊酮（MDPV）是几种合成卡西酮之一，是非法“浴盐”的常见成分。在利用雄性啮齿动物进行药物辨别方法的临床前研究中，MDPV 被描述为类似于可卡因和 3,4-亚甲基二氧甲基苯丙胺盐酸盐（MDMA）。虽然利用雌性大鼠进行药物辨别研究的情况较少，但目前的研究评估了 MDPV 在 12 只成年雌性 Sprague-Dawley 大鼠中的辨别刺激作用，这些大鼠在固定比率 20 的食物强化条件下，接受 0.5 mg/kg MDPV 与盐水的辨别训练。通过 MDPV 及其对映异构体、其他合成卡西酮[α-吡咯烷戊基苯酮盐酸盐（α-PVP）、4-甲基甲卡西酮（4-MMC）]、其他多巴胺激动剂（可卡因、[+]-甲基苯丙胺]和 5-羟色胺激动剂[MDMA、麦角酸二乙基酰胺（LSD）]评估了刺激替代作用。通过多巴胺 D1 受体拮抗剂 SCH23390 和 D2 受体拮抗剂氟哌啶醇评估了刺激拮抗作用。可卡因和[+]-甲基苯丙胺使 MDPV 产生完全的刺激概括，对反应率的影响最小。LSD 产生部分替代，而 MDMA 和 4-MMC 产生完全替代，所有这些 5-羟色胺能化合物都产生剂量依赖性的反应抑制。（S）-MDPV 和 α-PVP 产生完全替代，与外消旋体具有相似的效力，而（R）-MDPV 直至 5mg/kg 剂量都未能替代。SCH23390 和氟哌啶醇均减弱了低剂量 MDPV 的辨别作用，实质上使剂量-反应曲线向右移动，但未能阻断训练剂量的辨别。这些发现与以往仅基于雄性啮齿动物的报告基本一致。此外，它们证实了多巴胺能机制的贡献，但不能排除其他神经递质作用对 MDPV 内感受性刺激作用的可能贡献。
