Adolescent maturation of cocaine-sensitive neural mechanisms
Adolescent maturation of cocaine-sensitive neural mechanisms
复制标题
DOI：
10.1038/sj.npp.1301349
复制
发表时间：
2007-11-01
影响因子：
7.6
通讯作者：
Leslie, Frances M.
中科院分区：
文献类型：
--
作者：
Cao, Junran;Lotfipour, Shahrdad;Leslie, Frances M.
临床和动物研究都表明，青少年的中枢神经系统成熟较晚，这可能是青少年典型行为的基础。特别是，与成年人相比，青少年对可卡因的行为反应降低。在本研究中，可卡因被用作探索青少年大脑成熟的工具。幼年（出生后第27天（P））、青春期（P37）和成年（P90）雄性Sprague-Dawley大鼠用可卡因（750 μ g/kg/注射× 2，静脉内）进行急性处理，原位杂交检测神经元活化标志物c-fos mRNA表达。可卡因诱导的c-fos mRNA在不同年龄的尾壳核（CPu）、背侧核和终纹外侧床核中是相似的。相反，有一个减少的反应，在少年/青少年腹侧CPU和少年中央杏仁核，和少年/青少年皮层的反应增加。进一步的研究评估了可卡因反应在腹侧CPu的晚成熟的机制。在区域多巴胺（DA）转运蛋白结合方面没有观察到显著的年龄差异。虽然纹状体DA含量显着减少，在P27相比，成人，背侧和腹侧亚区之间没有差异。相比之下，基础和可卡因诱导的细胞外DA溢出，在体内微透析测量，是较低的少年腹侧CPU比成人。在背侧CPu中未观察到这种年龄差异。这些结果表明，冲动活动的DA传入腹侧CPu是不成熟的青少年。总之，本研究表明，可卡因敏感的神经元回路在青春期继续成熟。
Both clinical and animal studies have shown that adolescents undergo a late maturation of the central nervous system, which may underlie adolescent typical behaviors. In particular, decreased behavioral response to cocaine has been found in adolescents as compared to adults. In the present study, cocaine was used as a tool to explore adolescent brain maturation. Juvenile ( postnatal day ( P) 27), adolescent (P37), and adult (P90) male Sprague-Dawley rats were treated acutely with cocaine (750 mu g/kg/injection x 2,i.v.), and c-fos mRNA expression, a marker of neuronal activation, was evaluated by in situ hybridization. Cocaine-induced c-fos mRNA was similar across ages in the dorsal caudate putamen (CPu), nucleus accumbens, and lateral bed nucleus of the stria terminalis. In contrast, there was a diminished response in juvenile/adolescent ventral CPu and in juvenile central nucleus of the amygdala, and an increased response in juvenile/adolescent cortex. Further studies evaluated the mechanism of the late maturation of cocaine response in ventral CPu. No significant age differences were observed in regional dopamine (DA) transporter binding. Although striatal DA content was significantly reduced at P27 as compared to adult, there was no difference between dorsal and ventral subregions. In contrast, basal- and cocaine-induced extracellular DA overflow, as measured by in vivo microdialysis, was lower in juvenile ventral CPu than in the adults. This age difference was not observed in dorsal CPu. These findings suggest that impulse activity in DA afferents to ventral CPu is immature in adolescents. In conclusion, the present study showed that cocaine-sensitive neuronal circuits continue to mature during adolescence.