Behavioural Neuroscience Laboratory, Mental Health Research Institute, Melbourne, Australia.
Int J Neuropsychopharmacol. 2009 Nov;12(10):1383-93. doi: 10.1017/S1461145709000388. Epub 2009 Apr 29.
Neuregulin 1 (Nrg1) has been widely recognized as a candidate gene for schizophrenia. This study therefore investigated mice heterozygous for a mutation in the transmembrane domain of this trophic factor (Nrg1+/- mice) in a number of behavioural test systems with relevance to schizophrenia, including psychotropic drug-induced locomotor hyperactivity and prepulse inhibition (PPI) of startle. Baseline locomotor activity in the open field or in photocell cages was slightly, but significantly enhanced in Nrg1+/- mice compared to wild-type littermate controls at age 12-16 wk, but not at age 6 months. The ability of amphetamine, phencyclidine (PCP) or MK-801 to induce locomotor hyperactivity was not significantly different between the genotypes. There was no difference in baseline PPI, startle or startle habituation and there was no difference in the effect of apomorphine, amphetamine or MK-801 on any of these parameters. Only treatment with the 5-HT1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) showed a differential effect between genotypes, with a disruption of PPI occurring in Nrg1+/- mice compared to no effect in wild-type controls. This treatment also induced a significant reduction of startle which could have influenced the result. The density of dopamine D2 receptors in the forebrain and of 5-HT1A receptors in the hippocampus and raphe nuclei was not different between Nrg1+/- mice and controls. These studies add to the knowledge about behavioural effects in this mouse model of impaired Nrg1 function and suggest that a number of the behavioural tests with relevance to schizophrenia are normal in these mice.
神经调节蛋白 1(Nrg1)已被广泛认为是精神分裂症的候选基因。因此,本研究在与精神分裂症相关的多种行为测试系统中,研究了这种营养因子跨膜结构域发生突变的杂合子小鼠(Nrg1+/- 小鼠),包括精神药物诱导的运动过度和惊跳反射(PPI)。与野生型同窝对照相比,Nrg1+/- 小鼠在 12-16 周龄时在开阔场或光电笼中的基础运动活性略有但显著增强,但在 6 月龄时没有增强。安非他命、苯环利定(PCP)或 MK-801 诱导运动过度的能力在基因型之间没有显著差异。基础 PPI、惊跳或惊跳习惯化没有差异,阿扑吗啡、安非他命或 MK-801 对这些参数的任何影响也没有差异。只有 5-HT1A 受体激动剂 8-羟基-二丙基氨基四氢萘(8-OH-DPAT)的治疗显示出基因型之间的差异效应,与野生型对照相比,Nrg1+/- 小鼠的 PPI 中断。这种治疗还导致惊跳显著减少,这可能影响了结果。前脑多巴胺 D2 受体和海马和中缝核 5-HT1A 受体的密度在 Nrg1+/- 小鼠和对照之间没有差异。这些研究增加了对这种 Nrg1 功能受损小鼠模型行为影响的了解,并表明与精神分裂症相关的许多行为测试在这些小鼠中正常。