Lima Vivian C F, Molchanov Moriana L, Aguiar Daniele C, Campos Alline C, Guimarães Francisco Silveira
Department of Pharmacology, School of Medicine of Ribeirão Preto Campus, USP, 14049-900, Ribeirão Preto, SP, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jan 1;32(1):178-85. doi: 10.1016/j.pnpbp.2007.08.006. Epub 2007 Aug 15.
Glutamatergic neurotransmission in the dorsolateral periaqueductal gray (dlPAG) is related to defensive responses. However, the role of group I glutamate metabotropic receptors (mGluR) in these responses has been poorly investigated. The objective of the present study, therefore, was to test the hypothesis that interference with group I mGluR-mediated neurotransmission in dlPAG could modulate defensive responses. Male Wistar rats with cannulae aimed at the dlPAG were submitted to the following experiments: 1. intra dlPAG injections of vehicle (veh, 0.2 microL) or (RS)1-aminoindan-1,5-dicarboxylic acid (AIDA, 30-100 nmol, an mGluR1 receptor competitive antagonist) followed, 5 min later, by veh or trans-(+)-1-amino-1,3-ciclopentanedicarboxylic acid (tACPD, a group I and II mGluR agonist, 30 nmol); 2. intra-dlPAG injections of veh, AIDA (30 nmol) or 2-methyl-6-(phenylethynyl)-pyridine (MPEP, an mGluR5 receptor non-competitive antagonist, 50 nmol) followed by trans-azetidine-2,4-dicarboxylic acid (tADA, a group I mGluR agonist, 10 nmol); 3. and 4. intra-dlPAG injections of vehicle, AIDA (10-30 nmol) or MPEP (10-50 nmol) before the elevated plus maze (EPM) test; 5. intra-dlPAG injections of vehicle, AIDA (30 nmol) or MPEP (50 nmol) before the Vogel punished licking test. tACPD induced defensive responses characterized by jumps and an increased number of crossings in the observation box. These responses were attenuated by AIDA (30 nmol). tADA produced similar responses, although of lower intensity. tADA effects were prevented by AIDA and MPEP. Both drugs also produced anxiolytic-like effects in the EPM and Vogel tests when injected alone. The results suggest that group I metabotropic glutamate receptors in the dlPAG facilitate defensive responses and may also be involved in regulating anxiety-like behavior.
背外侧导水管周围灰质(dlPAG)中的谷氨酸能神经传递与防御反应有关。然而,I组代谢型谷氨酸受体(mGluR)在这些反应中的作用尚未得到充分研究。因此,本研究的目的是检验以下假设:干扰dlPAG中I组mGluR介导的神经传递可以调节防御反应。将带有插管并指向dlPAG的雄性Wistar大鼠进行以下实验:1. 向dlPAG内注射溶剂(veh,0.2微升)或(RS)1-氨基茚满-1,5-二羧酸(AIDA,30 - 100纳摩尔,一种mGluR1受体竞争性拮抗剂),5分钟后,再注射溶剂或反式(+)-1-氨基-1,3-环戊二羧酸(tACPD,一种I组和II组mGluR激动剂,30纳摩尔);2. 向dlPAG内注射溶剂、AIDA(30纳摩尔)或2-甲基-6-(苯乙炔基)吡啶(MPEP,一种mGluR5受体非竞争性拮抗剂,50纳摩尔),随后注射反式氮杂环丁烷-2,4-二羧酸(tADA,一种I组mGluR激动剂,10纳摩尔);3. 和4. 在高架十字迷宫(EPM)试验前向dlPAG内注射溶剂、AIDA(10 - 30纳摩尔)或MPEP(10 - 50纳摩尔);5. 在Vogel惩罚舔舐试验前向dlPAG内注射溶剂、AIDA(30纳摩尔)或MPEP(50纳摩尔)。tACPD诱导的防御反应表现为跳跃以及观察箱内穿越次数增加。这些反应被AIDA(30纳摩尔)减弱。tADA产生了类似的反应,尽管强度较低。AIDA和MPEP可阻止tADA的作用。这两种药物单独注射时在EPM和Vogel试验中也产生了抗焦虑样效应。结果表明,dlPAG中的I组代谢型谷氨酸受体促进防御反应,并且可能也参与调节焦虑样行为。