Uehara Takashi, Sumiyoshi Tomiki, Matsuoka Tadasu, Itoh Hiroko, Kurachi Masayoshi
Department of Neuropsychiatry, University of Toyama School of Medicine, 2630 Sugitani, Toyama 930-0194, Japan.
Psychopharmacology (Berl). 2006 Jun;186(2):218-25. doi: 10.1007/s00213-006-0370-y. Epub 2006 Apr 5.
Lactate has been shown to play a significant role in energy metabolism and reflect neural activity in the brain.
Using in vivo microdialysis technique, we measured extracellular lactate concentrations in the medial prefrontal cortex (mPFC) and the basolateral amygdaloid (BLA) nucleus of rats under electric foot shock stress. Moreover, to examine the role of serotonin (5-HT)(1A) receptors in brain energy metabolism in response to stressors, we attempted to determine whether the stress-induced changes of extracellular lactate levels in the mPFC and BLA are attenuated by tandospirone, a partial agonist at 5-HT(1A) receptors, or perospirone, a novel atypical antipsychotic with a 5-HT(1A) receptor partial agonist and 5-HT(2A)/dopamine-D(2) antagonist property.
Foot shock stress led to an increase in extracellular lactate concentrations both in the mPFC and BLA. Tandospirone (2 mg/kg) attenuated the foot shock stress-induced increase of extracellular lactate concentrations in both of the brain regions, which was blocked by pretreatment with WAY-100635, a selective 5-HT(1A) antagonist. On the other hand, perospirone (0.3 mg/kg) attenuated the increment of extracellular lactate concentrations in the mPFC and BLA, which was unaltered by pretreatment with WAY-100635.
These results indicate that the foot shock stress-induced increase in lactate metabolism is partly regulated by 5-HT(1A) receptors both in cortical and limbic regions.
乳酸已被证明在能量代谢中发挥重要作用,并反映大脑中的神经活动。
我们使用体内微透析技术,测量了电足部电击应激下大鼠内侧前额叶皮质(mPFC)和基底外侧杏仁核(BLA)核中的细胞外乳酸浓度。此外,为了研究5-羟色胺(5-HT)(1A)受体在应激源引起的脑能量代谢中的作用,我们试图确定5-HT(1A)受体的部分激动剂坦度螺酮或具有5-HT(1A)受体部分激动剂和5-HT(2A)/多巴胺-D(2)拮抗剂特性的新型非典型抗精神病药物哌罗匹隆是否能减弱应激诱导的mPFC和BLA中细胞外乳酸水平的变化。
足部电击应激导致mPFC和BLA中的细胞外乳酸浓度增加。坦度螺酮(2mg/kg)减弱了足部电击应激诱导的两个脑区细胞外乳酸浓度的增加,这一作用被选择性5-HT(1A)拮抗剂WAY-100635预处理所阻断。另一方面,哌罗匹隆(0.3mg/kg)减弱了mPFC和BLA中细胞外乳酸浓度的增加,而WAY-100635预处理并未改变这一作用。
这些结果表明,足部电击应激诱导的乳酸代谢增加在皮质和边缘区域均部分受5-HT(1A)受体调节。