Instituto de Investigaciones "Prof. Dr. Alberto C. Taquini"-ININCA, Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Ciudad de Buenos Aires, Argentina.
Synapse. 2013 Sep;67(9):553-67. doi: 10.1002/syn.21660. Epub 2013 May 2.
Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction.
围产期窒息（PA）增加了患多巴胺相关疾病的可能性，例如注意力缺陷多动障碍和精神分裂症。由于多巴胺能传递在可卡因敏化中起主要作用，本研究的目的是确定 PA 是否与可卡因行为敏化的改变有关。为此，阴道分娩的成年大鼠（CTL）、剖宫产（C+）或 C+ 合并 15 分钟（PA15，中度 PA）或 19 分钟（PA19，重度 PA）全身缺氧，反复接受可卡因（腹腔注射，15mg/kg），然后在 5 天戒断期后用可卡因（腹腔注射，15mg/kg）进行挑战。此外，评估了背侧（CPu）和腹侧（NAcc）纹状体中的 c-Fos、FosB/ΔFosB、DAT 和 TH 的表达。结果表明，PA15 大鼠对可卡因的运动敏化作用增强，而 PA19 大鼠对可卡因的运动敏化作用异常获得，且对可卡因无敏化反应。NAcc 中的 c-Fos 表达与可卡因敏化的这些改变有关，但 CPu 中的 c-Fos 表达与可卡因敏化的这些改变无关。在所有组和区域中，重复给予可卡因后，FosB/ΔFosB 的表达增加，尽管在 PA19 大鼠中表达水平较低。在 CTL、C+和 PA15 大鼠中，但在 PA19 大鼠中，NAcc 中的 TH 表达在反复接受可卡因治疗的组中减少，与挑战测试无关。此外，PA15 大鼠中的这种减少更为明显。在所有研究的组和区域中，DAT 的表达均保持不变。这些结果表明，中度 PA 可能增加对药物滥用的易感性，特别是对可卡因成瘾的易感性。
