Carneiro de Oliveira Paulo E, Leão Rodrigo M, Bianchi Paula C, Marin Marcelo T, Planeta Cleopatra da Silva, Cruz Fábio C
Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University-UNESP Araraquara, Brazil.
Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University-UNESPAraraquara, Brazil; Joint Graduate Program in Physiological Sciences, UFSCar/UNESP, Faculdade de Odontologia de AraraquaraAraraquara, Brazil.
Front Behav Neurosci. 2016 Sep 12;10:173. doi: 10.3389/fnbeh.2016.00173. eCollection 2016.
While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.
虽然临床和临床前证据表明青春期是成瘾发展的风险期,但其潜在的神经机制在很大程度上尚不清楚。青春期的应激对药物成瘾有巨大影响。然而,关于应激、青春期和成瘾之间相互作用的相关机制却知之甚少。研究指出ΔFosB可能是这一现象的一个靶点。在本研究中,将青春期和成年大鼠(分别为出生后第28天和60天)每天束缚2小时,持续7天。在它们最后一次暴露于应激后3天,用生理盐水或苯丙胺(1.0mg/kg腹腔注射)对动物进行激发,并记录苯丙胺诱导的运动。行为测试后立即将大鼠断头,解剖伏隔核以测量ΔFosB蛋白水平。我们发现,重复束缚应激增加了成年和青春期大鼠中苯丙胺诱导的运动。此外,在成年大鼠中,应激诱导的运动敏化与伏隔核中ΔFosB表达增加有关。我们的数据表明,ΔFosB可能参与了成年大鼠中与应激诱导的对苯丙胺交叉敏化相关的一些神经元可塑性变化。