Ago Y, Sakaue M, Baba A, Matsuda T
Laboratory of Medicinal Pharmacology, and Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
J Neurochem. 2002 Oct;83(2):353-9. doi: 10.1046/j.1471-4159.2002.01128.x.
Serotonin (5-HT)1A receptors modulate in vivo release of brain monoaminergic neurotransmitters which may be involved in isolation-induced aggressive behavior. The present study examined the effect of isolation rearing on the 5-HT1A receptor-mediated modulation of dopamine (DA), 5-HT and noradrenaline (NA) release in the frontal cortex of mice. The selective 5-HT1A receptor agonist (S)-5-[-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242) increased the release of DA and NA and decreased the release of 5-HT in the frontal cortex of mice. The effect of MKC-242 on DA release was significantly less in isolation-reared mice than in group-reared mice, while effects of the drug on NA and 5-HT release did not differ between both groups. The effect of the other 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin on cortical DA release was also less in isolation-reared mice than in group-reared mice, and that of the drug on cortical 5-HT release did not differ between both groups. In contrast to MKC-242-induced DA release, amphetamine-induced increase in cortical DA release in vivo was greater in isolation-reared mice. The present findings suggest that isolation rearing enhances the activity of cortical dopaminergic neurons and reduces selectively the 5-HT1A receptor-mediated release of DA in the cortex.
血清素(5-羟色胺,5-HT)1A受体调节脑单胺能神经递质的体内释放,这可能与隔离诱导的攻击行为有关。本研究检测了隔离饲养对小鼠额叶皮质中5-HT1A受体介导的多巴胺(DA)、5-HT和去甲肾上腺素(NA)释放调节的影响。选择性5-HT1A受体激动剂(S)-5-[-[(1,4-苯并二恶烷-2-基甲基)氨基]丙氧基]-1,3-苯并二恶烷盐酸盐(MKC-242)增加了小鼠额叶皮质中DA和NA的释放,并减少了5-HT的释放。MKC-242对DA释放的作用在隔离饲养的小鼠中明显小于群居饲养的小鼠,而该药物对NA和5-HT释放的作用在两组之间没有差异。另一种5-HT1A受体激动剂8-羟基-2-(二正丙基氨基)四氢萘对皮质DA释放的作用在隔离饲养的小鼠中也小于群居饲养的小鼠,且该药物对皮质5-HT释放的作用在两组之间没有差异。与MKC-242诱导的DA释放相反,苯丙胺诱导的体内皮质DA释放增加在隔离饲养的小鼠中更大。本研究结果表明,隔离饲养增强了皮质多巴胺能神经元的活性,并选择性地减少了5-HT1A受体介导的皮质DA释放。