Lipska B K, Weinberger D R
Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Neuroscience Center, St. Elizabeths, Washington, DC 20032.
Brain Res Dev Brain Res. 1993 Oct 15;75(2):213-22. doi: 10.1016/0165-3806(93)90026-7.
The developmental effects of neonatal excitotoxic ventral hippocampal (VH) damage on behaviors related to dopaminergic (DA) transmission in the basal ganglia were investigated in the rat. Ibotenic acid (in Lesion) or artificial cerebrospinal fluid (in Sham) was infused into the VH of 7-day-old (PD7) rat pups. Haloperidol-induced (1 mg/kg, i.p.) catalepsy and apomorphine-induced (0.75 mg/kg, s.c.) stereotypic behaviors as well as locomotion were assessed in Sham and Lesion rats prior to (PD35) and after puberty (PD56). On PD35, Lesion and Sham animals did not differ in induced catalepsy or stereotypy. On PD56, however, Lesion animals were less cataleptic following haloperidol injection and manifested supersensitivity to apomorphine as compared to Sham rats. At both, PD35 and PD56, locomotor activity after apomorphine was significantly increased in Lesion animals as compared with controls. These results indicate that the neonatal excitotoxic VH lesion results in a unique time-dependent pattern of behavioral changes related to striatal DA transmission. Moreover, the response to apomorphine differs qualitatively from that previously reported after the analogous lesion induced in adult animals in which stereotypy was reduced. These findings suggest that early hippocampal deafferentation affects the development of other brain regions, such as the medial prefrontal cortex, that are also involved in the regulation of striatal DA function.
在大鼠中研究了新生期兴奋性毒性腹侧海马（VH）损伤对与基底神经节中多巴胺能（DA）传递相关行为的发育影响。将鹅膏蕈氨酸（损伤组）或人工脑脊液（假手术组）注入7日龄（出生后第7天，PD7）的幼鼠VH中。在青春期前（PD35）和青春期后（PD56）评估假手术组和损伤组大鼠中氟哌啶醇诱导的（1mg/kg，腹腔注射）僵住症和阿扑吗啡诱导的（0.75mg/kg，皮下注射）刻板行为以及运动能力。在PD35时，损伤组和假手术组动物在诱导的僵住症或刻板行为方面没有差异。然而，在PD56时，与假手术组大鼠相比，损伤组动物在注射氟哌啶醇后僵住症较轻，并且对阿扑吗啡表现出超敏反应。在PD35和PD56时，与对照组相比，损伤组动物在注射阿扑吗啡后的运动活性均显著增加。这些结果表明，新生期兴奋性毒性VH损伤导致与纹状体DA传递相关的行为变化呈现独特的时间依赖性模式。此外，对阿扑吗啡的反应在性质上与先前在成年动物中诱导类似损伤后报道的反应不同，成年动物中刻板行为减少。这些发现表明，早期海马去传入影响了其他脑区的发育，如内侧前额叶皮质，其也参与纹状体DA功能的调节。
