Schiavi Sara, Melancia Francesca, Carbone Emilia, Buzzelli Valeria, Manduca Antonia, Peinado Patricia Jiménez, Zwergel Clemens, Mai Antonello, Campolongo Patrizia, Vanderschuren Louk J M J, Trezza Viviana
Department of Science, University "Roma Tre", Rome, Italy.
Department of Drug Chemistry & Technologies, Sapienza University of Rome, Rome, Italy.
Neuropsychopharmacology. 2020 Nov;45(12):2012-2019. doi: 10.1038/s41386-020-0729-5. Epub 2020 Jun 7.
Methylenedioxypyrovalerone (MDPV) is the most popular synthetic cathinone found in products marketed as 'bath salts', widely abused among teenagers and young adults. Synthetic cathinones have pharmacological effects resembling those of psychostimulants, which are known to disrupt a variety of social behaviors. However, despite the popular use of MDPV by young people in social contexts, information about its effects on social behavior is scarce. To investigate the impact of MDPV on social behavior at young age, and the underlying neurobehavioral mechanisms, we focused on social play behavior. Social play behavior is the most characteristic social behavior displayed by young mammals and it is crucial for neurobehavioral development. Treatment with MDPV reduced social play behavior in both juvenile and young adult male rats, and its play-suppressant effect was subject to tolerance but not sensitization. As the behavioral effects of MDPV have been ascribed to dopaminergic and noradrenergic neurotransmission, and given the role of these neurotransmitters in social play, we investigated the involvement of dopamine and noradrenaline in the play-suppressant effects of MDPV. The effects of MDPV on social play were blocked by either the α2 adrenoceptor antagonist RX821002 or the dopamine receptor antagonist flupenthixol, given alone or together at sub-effective doses. In sum, MDPV selectively suppresses the most vigorous social behavior of developing rats through both noradrenergic and dopaminergic mechanisms. This study provides important preclinical evidence of the deleterious effects of MDPV on social behavior, and as such increases our understanding of the neurobehavioral effects of this popular cathinone.
亚甲基二氧吡咯戊酮(MDPV)是在以“浴盐”销售的产品中发现的最常见的合成卡西酮,在青少年和年轻人中广泛滥用。合成卡西酮具有类似于精神兴奋剂的药理作用,已知会扰乱多种社会行为。然而,尽管年轻人在社交场合中普遍使用MDPV,但关于其对社会行为影响的信息却很少。为了研究MDPV对幼年社会行为的影响及其潜在的神经行为机制,我们重点关注了社会玩耍行为。社会玩耍行为是幼年哺乳动物表现出的最具特征性的社会行为,对神经行为发育至关重要。用MDPV处理可减少幼年和成年雄性大鼠的社会玩耍行为,其玩耍抑制作用会产生耐受性但不会产生敏化作用。由于MDPV的行为效应归因于多巴胺能和去甲肾上腺素能神经传递,并且鉴于这些神经递质在社会玩耍中的作用,我们研究了多巴胺和去甲肾上腺素在MDPV玩耍抑制作用中的参与情况。单独或以亚有效剂量联合给予α2肾上腺素能受体拮抗剂RX821002或多巴胺受体拮抗剂氟哌噻吨,均可阻断MDPV对社会玩耍的影响。总之,MDPV通过去甲肾上腺素能和多巴胺能机制选择性地抑制发育中大鼠最活跃的社会行为。这项研究提供了MDPV对社会行为有害影响的重要临床前证据,从而增加了我们对这种流行卡西酮神经行为效应的理解。