Brown Russell W, Perna Marla K, Noel Daniel M, Whittemore Jamie D, Lehmann Julia, Smith Meredith L
Department of Psychology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Behav Pharmacol. 2011 Aug;22(4):374-8. doi: 10.1097/FBP.0b013e328348737b.
Neonatal quinpirole treatment has been shown to produce an increase in dopamine D2-like receptor sensitivity that persists throughout the subject's lifetime. The objective was to analyze the effects of neonatal quinpirole treatment on effects of amphetamine in adolescent rats using locomotor sensitization and conditioned place preference procedures. Sprague-Dawley rats were treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1 to P11 and raised to adolescence. For locomotor sensitization, subjects were given amphetamine (1 mg/kg) or saline every second day from P35 to P47 and were placed into a locomotor arena. In female rats, neonatal quinpirole treatment enhanced amphetamine locomotor sensitization compared with quinpirole-free controls sensitized to amphetamine. Male rats demonstrated sensitization to amphetamine, although this was muted compared with female rats, and were unaffected by neonatal quinpirole. For conditioned place preference, subjects were conditioned for 8 consecutive days (P32-39) with amphetamine (1 mg/kg) or saline and a drug-free preference test was conducted at P40. Rats treated with neonatal quinpirole enhanced time spent in the amphetamine-paired context compared with quinpirole-free controls conditioned with amphetamine, but only female controls conditioned with amphetamine spent more time in the drug-paired context compared with saline-treated controls. Increased D₂-like receptor sensitivity appears to have enhanced the behavioral effects of amphetamine, but these effects were more prevalent in adolescent female rats compared with male rats.
已证明新生儿使用喹吡罗治疗会使多巴胺 D2 样受体敏感性增加,且这种增加会持续至个体终生。本研究的目的是使用运动敏化和条件性位置偏爱程序,分析新生儿喹吡罗治疗对青春期大鼠苯丙胺作用的影响。将 Sprague-Dawley 大鼠从出生后第 1 天(P1)至第 11 天用喹吡罗(1 mg/kg)或生理盐水进行处理,然后饲养至青春期。对于运动敏化实验,从 P35 至 P47,每隔一天给实验对象注射苯丙胺(1 mg/kg)或生理盐水,并将其放入运动 arena 中。在雌性大鼠中,与未用喹吡罗处理且对苯丙胺敏感的对照组相比,新生儿期用喹吡罗治疗增强了苯丙胺诱导的运动敏化。雄性大鼠对苯丙胺也表现出敏化,尽管与雌性大鼠相比这种敏化较弱,且不受新生儿期喹吡罗处理的影响。对于条件性位置偏爱实验,实验对象在 P32 - 39 连续 8 天用苯丙胺(1 mg/kg)或生理盐水进行条件化处理,并在 P40 进行无药物偏爱测试。与用苯丙胺进行条件化处理的未用喹吡罗的对照组相比,新生儿期用喹吡罗治疗的大鼠在与苯丙胺配对的环境中停留的时间增加,但只有用苯丙胺进行条件化处理的雌性对照组与用生理盐水处理的对照组相比,在与药物配对的环境中停留的时间更长。D₂样受体敏感性增加似乎增强了苯丙胺的行为效应,但与雄性大鼠相比,这些效应在青春期雌性大鼠中更为普遍。