Yamamoto K, Ozawa N, Shinba T, Hoshino T
Department of Neurophysiology, Tokyo Institute of Psychiatry, Japan.
Schizophr Res. 1994 Sep;13(2):145-50. doi: 10.1016/0920-9964(94)90095-7.
Pharmacological studies on neuroleptics and amphetamine strongly suggest that some dysfunction of the central catecholamine system may play a key role in the pathogenesis of schizophrenia. Our previous studies have demonstrated that intraventricular administration of 6-hydroxydopamine, a selective neurotoxin of the catecholamine neuron, can reproduce schizophrenia-like abnormalities in the skin conductance activity. In the present experiments, effects of pharmacological modulation of the central noradrenergic activity were studied in rats. Stimulation of the central noradrenergic activity by yohimbine (0.6 mg/kg, i.m.) slowed down the habituation of the skin conductance response (SCR) and increase the spontaneous fluctuation of the skin conductance (SF), while inhibition of the activity by clonidine (0.06 mg/kg, i.m.) accelerated or obliterated the SCR and decreased the SF frequency. If the functional significance of the central noradrenergic system lies in vigilance control, the present results are consistent with classical theory in psychophysiology: the habituation rate of SCR and the frequency of SF are correlated well with each other and both indices reflect arousal level. The disorder of the system should produce not only these psychophysiological abnormalities but also psychological disturbances; i.e., overarousal and underarousal syndromes. Therefore, the dysfunction of the noradrenergic system might constitute an essential aspect of schizophrenic disorder.
对神经阻滞剂和苯丙胺的药理学研究有力地表明,中枢儿茶酚胺系统的某些功能障碍可能在精神分裂症的发病机制中起关键作用。我们之前的研究表明,脑室内注射儿茶酚胺神经元的选择性神经毒素6-羟基多巴胺,可在皮肤电导活动中重现类似精神分裂症的异常。在本实验中,研究了对大鼠中枢去甲肾上腺素能活性进行药理学调节的作用。育亨宾(0.6毫克/千克,肌肉注射)刺激中枢去甲肾上腺素能活性会减缓皮肤电导反应(SCR)的习惯化,并增加皮肤电导的自发波动(SF),而可乐定(0.06毫克/千克,肌肉注射)抑制该活性则会加速或消除SCR,并降低SF频率。如果中枢去甲肾上腺素能系统的功能意义在于警觉控制,那么目前的结果与心理生理学的经典理论一致:SCR的习惯化率和SF频率相互之间密切相关,且这两个指标均反映觉醒水平。该系统的紊乱不仅应产生这些心理生理异常,还应导致心理障碍,即过度觉醒和觉醒不足综合征。因此,去甲肾上腺素能系统的功能障碍可能构成精神分裂症的一个重要方面。