1Laboratório de Neuropsicofarmacologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
J Psychopharmacol. 2013 Dec;27(12):1160-8. doi: 10.1177/0269881113482840. Epub 2013 Mar 27.
Intra-dorsal hippocampus (DH) injections of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin-1A (5-hydroxytryptamine (5-HT)-1A) receptor agonist, were previously shown to inhibit the expression of contextual fear when administered six hours after conditioning. However, further understanding of the consolidation and expression of aversive memories requires investigations of these and other mechanisms at distinct time points and the regions of the brain to which they are transferred. Thus, the purpose of the present study was to investigate the role of DH serotonergic and γ-aminobutyric acid (GABA)ergic mechanisms in the expression of contextual fear 24 h after conditioning, reflected by fear-potentiated startle (FPS) and freezing behavior. The recruitment of the amygdala and medial prefrontal cortex (mPFC) in these processes was also evaluated by measuring Fos protein immunoreactivity. Although intra-DH injections of 8-OH-DPAT did not produce behavioral changes, muscimol reduced both FPS and the freezing response. Fos protein immunoreactivity revealed that contextual fear promoted wide activation of the mPFC, which was significantly reduced after intra-DH infusions of muscimol. The present findings, together with previous data, indicate that in contrast to 5-HT, which appears to play a role during the early phases of contextual aversive memory consolidation, longer-lasting GABA-mediated mechanisms are recruited during the expression of contextual fear memories.
内侧背海马(DH)注射 8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT),一种 5-羟色胺-1A(5-HT-1A)受体激动剂,先前的研究表明,在条件作用后 6 小时给药时,可抑制情境恐惧的表达。然而,进一步了解厌恶记忆的巩固和表达需要在不同的时间点和它们转移到的大脑区域研究这些和其他机制。因此,本研究的目的是研究 DH 血清素能和γ-氨基丁酸(GABA)能机制在条件作用后 24 小时表达情境恐惧中的作用,通过恐惧增强的惊跳(FPS)和冻结行为来反映。还通过测量 Fos 蛋白免疫反应性来评估杏仁核和内侧前额叶皮层(mPFC)在这些过程中的募集情况。尽管 DH 内注射 8-OH-DPAT 没有产生行为变化,但 muscimol 减少了 FPS 和冻结反应。Fos 蛋白免疫反应性显示,情境恐惧促进了 mPFC 的广泛激活,而在 muscimol 注入 DH 后,这种激活显著减少。这些发现与以前的数据一起表明,与似乎在情境性厌恶记忆巩固的早期阶段发挥作用的 5-HT 相反,在情境恐惧记忆的表达过程中,会募集到更长时间的 GABA 介导的机制。