Semenova Svetlana, Markou Athina
Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093-0603, USA.
Neuropharmacology. 2007 Mar;52(3):863-72. doi: 10.1016/j.neuropharm.2006.10.003. Epub 2006 Nov 28.
Schizophrenia is characterized by attentional deficits possibly associated with glutamate dysfunction. The role of postsynaptic metabotropic glutamate 5 receptors (mGluR5) or presynaptic inhibitory mGluR2/3 on attention is currently unknown. We investigated the effects of the mGluR5 antagonist MPEP (2-methyl-6[phenylethynyl]-pyridine) and the mGluR2/3 antagonist LY341495 on attention in the 5-choice serial reaction time task (5CSRTT), as well as on food intake to evaluate their effects on food motivation. The effects of pre-feeding and the muscle relaxant curare were examined to characterize the effects of alterations in the motivation or ability to perform the task, respectively. MPEP had no effect on accuracy but overall decreased performance in the 5CSRTT, including decreased speed of responding and decreased premature responses. LY341495 had no significant effect on rats' performance in the 5CSRTT. LY341495 decreased food intake in the home cage to a greater extent than MPEP. Curare decreased the speed of correct responding, reflecting motor impairment. Free feeding decreased overall performance, number of trials completed and number of head entries into the feeder, reflecting decreased motivation to perform the task. Thus, blockade of mGluR5, but not mGluR2/3, decreased overall responding without affecting accuracy in the 5CSRTT.
精神分裂症的特征是注意力缺陷,这可能与谷氨酸功能障碍有关。目前尚不清楚突触后代谢型谷氨酸受体5(mGluR5)或突触前抑制性mGluR2/3对注意力的作用。我们研究了mGluR5拮抗剂MPEP(2-甲基-6-[苯乙炔基]-吡啶)和mGluR2/3拮抗剂LY341495在5选串行反应时任务(5CSRTT)中对注意力的影响,以及对食物摄入量的影响,以评估它们对食物动机的作用。分别研究了预喂食和肌肉松弛剂箭毒的影响,以表征动机改变或执行任务能力改变的影响。MPEP对准确性没有影响,但总体上降低了5CSRTT中的表现,包括反应速度降低和过早反应减少。LY341495对大鼠在5CSRTT中的表现没有显著影响。LY341495比MPEP更能降低笼内食物摄入量。箭毒降低了正确反应的速度,反映了运动障碍。自由进食降低了总体表现、完成的试验次数和进入喂食器的头部次数,反映了执行任务的动机降低。因此,阻断mGluR5而非mGluR2/3会降低总体反应,而不影响5CSRTT中的准确性。