Department of Psychology, California State University, 5500 University Parkway, San Bernardino, CA, 92407, USA.
Psychopharmacology (Berl). 2014 Oct;231(21):4167-77. doi: 10.1007/s00213-014-3561-y. Epub 2014 Apr 17.
The neural mechanisms mediating the ontogeny of behavioral sensitization are poorly understood.
The purpose of the present study was to determine the role of the D1 receptor for the induction of dopamine agonist-induced behavioral sensitization during the preweanling period.
In the first experiment, the early ontogeny of R-propylnorapomorphine (NPA)-induced behavioral sensitization was examined by pretreating male and female rats with saline or NPA (0.5, 1, or 2 mg/kg, intraperitoneally (IP)) before placement in activity chambers on postnatal day (PD) 12, 16, 20, or 24. One day later, rats were tested with lower doses of NPA and the occurrence of locomotor sensitization was determined. In subsequent experiments, rats were injected with saline or the D1 receptor antagonist SCH23390 (0.1, 0.5, 1, or 5 mg/kg, IP) 0, 15, 30, or 60 min before cocaine, methamphetamine (METH), or NPA pretreatment. The next day, rats were tested with the same dopamine agonist again and sensitized responding was assessed.
NPA produced one-trial behavioral sensitization at all ages tested. In preweanling rats, SCH23390, regardless of dose, was ineffective at preventing the induction of cocaine-, METH-, or NPA-induced one-trial behavioral sensitization.
The present results are in partial contrast to adult rodent studies, in which SCH23390 blocks the induction of METH- and apomorphine-induced behavioral sensitization, but not cocaine sensitization. When these findings are considered together, it appears that D1 receptor stimulation is not necessary for the induction of behavioral sensitization during the preweanling period, although D1 receptors may play a more important role in adulthood.
介导行为敏化发生的神经机制尚未完全阐明。
本研究旨在确定 D1 受体在幼年期多巴胺激动剂诱导的行为敏化中的作用。
在第一项实验中,通过在产后第 12、16、20 或 24 天将雄性和雌性大鼠用盐水或 R-丙基去甲那莫金(NPA)(0.5、1 或 2mg/kg,腹膜内注射)预处理,然后放入活动室,来检查 NPA 诱导的行为敏化的早期发生。一天后,用较低剂量的 NPA 测试大鼠,并确定运动敏化的发生。在随后的实验中,大鼠被注射盐水或 D1 受体拮抗剂 SCH23390(0.1、0.5、1 或 5mg/kg,腹膜内注射)0、15、30 或 60 分钟,然后用可卡因、甲基苯丙胺(METH)或 NPA 预处理。第二天,大鼠再次用相同的多巴胺激动剂进行测试,并评估敏化反应。
NPA 在所有测试的年龄都产生了一次性行为敏化。在幼年期大鼠中,无论剂量如何,SCH23390 均不能预防可卡因、METH 或 NPA 诱导的一次性行为敏化的诱导。
本研究结果与成年啮齿动物研究部分矛盾,在成年啮齿动物研究中,SCH23390 阻断了 METH 和阿扑吗啡诱导的行为敏化的诱导,但不能阻断可卡因敏化的诱导。当考虑到这些发现时,似乎在幼年期,D1 受体刺激对于行为敏化的诱导并不是必需的,尽管 D1 受体在成年期可能发挥更重要的作用。