Fujishiro Hiroshige, Umegaki Hiroyuki, Suzuki Yusuke, Oohara-Kurotani Shinobu, Yamaguchi Yoko, Iguchi Akihisa
Department of Geriatrics, Medicine in Growth and Aging, Program in Health and Community Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Nagoya, Aichi, 466-8550, Japan.
Psychopharmacology (Berl). 2005 Oct;182(2):253-61. doi: 10.1007/s00213-005-0072-x. Epub 2005 Oct 19.
The role of the hippocampal dopaminergic system in mnemonic function has not been clarified yet.
We previously reported that the dopamine D2 receptor (D2R) is involved in the regulation of acethylcholin (ACh) release in the hippocampus. In this study, we further investigated ACh-dopamine (DA) interaction in the hippocampus and its involvement in mnemonic function.
For experiment 1, rats fed with Cholin (Ch)-deficient chow were used. We examined the effects of D2R antagonist, raclopride, on cognitive performance using a passive avoidance task. We further carried out in vivo microdialysis to assess the effect of infusion of D2R agonist, quinpirole, into the ventral hippocampus on its capacity to release ACh. For experiment 2, rats fed with normal chow were used. The performance of a radial arm maze task was assessed to examine the effects of hippocampal injection of D2R agonist, quinpirole, on memory impairment induced by scopolamine, a muscarinic ACh antagonist.
In experiment 1, rats fed with Ch-deficient chow showed impaired performances indicated by prolonged latency on retention trials of a passive avoidance task following the hippocampal injection of D2R antagonist, and showed reduced capacity to release ACh following the injection of D2R agonist compared with rats fed with normal chow. In experiment 2, memory impairment induced by the intraperitoneal injection of scopolamine was ameliorated by the injection of D2R agonist into the ventral hippocampus.
These results indicate the possible involvement of hippocampal ACh-DA interaction in mnemonic processing.
海马多巴胺能系统在记忆功能中的作用尚未阐明。
我们之前报道过多巴胺D2受体(D2R)参与海马中乙酰胆碱(ACh)释放的调节。在本研究中,我们进一步研究了海马中ACh-多巴胺(DA)的相互作用及其在记忆功能中的作用。
实验1使用喂食胆碱(Ch)缺乏饲料的大鼠。我们使用被动回避任务检查D2R拮抗剂雷氯必利对认知能力的影响。我们进一步进行了体内微透析,以评估向腹侧海马注入D2R激动剂喹吡罗对其释放ACh能力的影响。实验2使用喂食正常饲料的大鼠。评估放射状臂迷宫任务的表现,以检查海马注射D2R激动剂喹吡罗对毒蕈碱型ACh拮抗剂东莨菪碱诱导的记忆损伤的影响。
在实验1中,喂食Ch缺乏饲料的大鼠在海马注射D2R拮抗剂后被动回避任务的保留试验中潜伏期延长,表明其表现受损,并且与喂食正常饲料的大鼠相比,注射D2R激动剂后释放ACh的能力降低。在实验2中,腹侧海马注射D2R激动剂改善了腹腔注射东莨菪碱引起的记忆损伤。
这些结果表明海马ACh-DA相互作用可能参与记忆加工。