Tai Yueh-Ming, Ko Chih-Yuan, Lin Chen-Cheng, Wan Yu-Yue, Chung Jing-Yi, Liu Yia-Ping
Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Respiratory Medicine Center of Fujian Province, Quanzhou, China.
Psychiatry Investig. 2018 Feb;15(2):193-199. doi: 10.30773/pi.2017.05.14.2. Epub 2017 Nov 7.
Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions.
Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured.
Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition.
The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.
中枢5-羟色胺1A(5-HT1A)受体参与感觉运动门控功能的调节。然而,在感觉运动门控能力受损的发育性社会剥夺(隔离饲养,IR)大鼠中,其确切作用尚未明确界定。因此,我们旨在研究在突触前5-羟色胺(5-HT)功能受损的情况下,5-HT1A激活对IR大鼠听觉惊吓反应(ASR)和前脉冲抑制(PPI)的影响。
社会对照(SOC)和IR大鼠接受脑室内(ICV)注射5-HT耗竭剂5,7-二氢色胺(5,7-DHT)。7天后,大鼠进入8-羟基二丙胺(8-OH-DPAT,一种5-HT1A激动剂)实验方案,测量其运动活性、ASR和PPI以及它们的5-HT组织水平。
我们的结果发现,IR和5,7-DHT均降低了5-HT的组织浓度。IR诱导的多动和门控损伤不受5-HT耗竭的影响。8-OH-DPAT增强了IR大鼠而非SOC大鼠的ASR,药物降低的PPI可通过5,7-DHT预处理进行调节。100μg/kg的8-OH-DPAT增强了5-HT耗竭的SOC大鼠的PPI。然而,对于IR大鼠,8-OH-DPAT在假手术大鼠中增强了PPI,但在耗竭状态下降低了PPI。
中枢5-HT系统的完整性对于隔离饲养大鼠中5-HT1A调节的感觉运动门控很重要。