Montagud-Romero Sandra, Nuñez Cristina, Blanco-Gandia M Carmen, Martínez-Laorden Elena, Aguilar María A, Navarro-Zaragoza Javier, Almela Pilar, Milanés Maria-Victoria, Laorden María-Luisa, Miñarro José, Rodríguez-Arias Marta
Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain.
Murcia Research Institute of Health Sciences (IMIB) and Faculty of Medicine, University of Murcia, Murcia, Spain.
Psychopharmacology (Berl). 2017 Jul;234(13):2063-2075. doi: 10.1007/s00213-017-4612-y. Epub 2017 May 2.
Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents.
The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice.
Male adolescent and young adult OF1 mice were exposed to four episodes of social defeat and were conditioned 3 weeks later with 1 mg/kg of cocaine. In a second set of mice, the expressions of the abovementioned dopaminergic and proBDNF and TrkB receptor were measured in VTA and NAc, respectively.
Adolescent mice experienced social defeats less intensely than their adult counterparts and produced lower levels of corticosterone. However, both adult and adolescent defeated mice developed conditioned place preference for the compartment associated with this low dose of cocaine. Furthermore, only adolescent defeated mice displayed diminished levels of the transcription factors Pitx3 in the VTA, without changes in the expression of DAT and D2DR in the NAc. In addition, stressed adult mice showed a decreased expression of proBDNF and the TrkB receptor, while stressed adolescent mice exhibited increased expression of latter without changes in the former.
Our findings suggest that dopaminergic pathways and proBDNF signaling and TrkB receptors play different roles in social defeat-stressed mice exposed to cocaine.
反复社会挫败（RSD）会增强可卡因对青少年和成年啮齿动物的奖赏效应。
本研究旨在比较RSD对成年和青少年小鼠可卡因条件性奖赏效应、腹侧被盖区（VTA）转录因子Pitx3和Nurr1水平、多巴胺转运体（DAT）、D2多巴胺受体（D2DR）以及脑源性神经营养因子前体（proBDNF）信号通路和伏隔核（NAc）中原肌球蛋白相关激酶B（TrkB）受体的长期影响。
雄性青少年和年轻成年OF1小鼠经历四次社会挫败，3周后用1mg/kg可卡因进行条件化训练。在另一组小鼠中，分别测量VTA和NAc中上述多巴胺能、proBDNF和TrkB受体的表达。
青少年小鼠经历的社会挫败比成年小鼠轻，皮质酮水平也较低。然而，成年和青少年受挫小鼠都对与低剂量可卡因相关的隔室产生了条件性位置偏好。此外，只有青少年受挫小鼠VTA中转录因子Pitx3水平降低，NAc中DAT和D2DR的表达没有变化。此外，应激成年小鼠proBDNF和TrkB受体表达降低，而应激青少年小鼠后者表达增加，前者无变化。
我们的研究结果表明，多巴胺能通路、proBDNF信号和TrkB受体在暴露于可卡因的社会挫败应激小鼠中发挥不同作用。
