Umeda Kenta, Suemaru Katsuya, Todo Nobuko, Egashira Nobuaki, Mishima Kenichi, Iwasaki Katsunori, Fujiwara Michihiro, Araki Hiroaki
Department of Neuropharmacology Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Eur J Pharmacol. 2006 Dec 28;553(1-3):157-62. doi: 10.1016/j.ejphar.2006.09.050. Epub 2006 Sep 28.
The prepulse inhibition of the startle response provides an operational measure of sensorimotor gating in which a weak stimulus presented prior to a startling stimulus reduces the startle response. Prepulse inhibition deficits were observed in patients with several neuropsychiatric disorders, including schizophrenia and acute manic bipolar patients. Valproic acid, carbamazepine and lithium carbonate are frequently used as mood stabilizers in patients with bipolar affective disorder and schizophrenia. However, little is known about the mechanisms of action of mood stabilizers on prepulse inhibition deficits. In this study, we investigated the effects of mood stabilizers on the disruption of prepulse inhibition of the acoustic startle response induced by either apomorphine or dizocilpine in mice. Valproate (30-300 mg/kg, i.p.), carbamazepine (3-30 mg/kg, i.p.) and lithium carbonate (10-100 mg/kg, p.o.) had any effect on prepulse inhibition by itself. Valproate, carbamazepine and lithium carbonate reversed the disruption of prepulse inhibition induced by apomorphine (1 mg/kg, s.c.). Although valproate and carbamazepine had no effect on the disruption of prepulse inhibition induced by dizocilpine (0.3 mg/kg, s.c.), lithium carbonate exacerbated the dizocilpine-induced disruption. These results suggest that valproate, carbamazepine and lithium carbonate reverse the disruption of prepulse inhibition through the dopaminergic system.
惊吓反应的前脉冲抑制为感觉运动门控提供了一种操作性测量方法，即在惊吓刺激之前呈现的弱刺激会降低惊吓反应。在包括精神分裂症和急性躁狂双相情感障碍患者在内的几种神经精神疾病患者中观察到前脉冲抑制缺陷。丙戊酸、卡马西平和碳酸锂经常被用作双相情感障碍和精神分裂症患者的情绪稳定剂。然而，关于情绪稳定剂对前脉冲抑制缺陷的作用机制知之甚少。在本研究中，我们研究了情绪稳定剂对阿扑吗啡或地佐环平诱导的小鼠听觉惊吓反应前脉冲抑制破坏的影响。丙戊酸盐（30 - 300毫克/千克，腹腔注射）、卡马西平（3 - 30毫克/千克，腹腔注射）和碳酸锂（10 - 100毫克/千克，口服）自身对前脉冲抑制没有任何影响。丙戊酸盐、卡马西平和碳酸锂逆转了阿扑吗啡（1毫克/千克，皮下注射）诱导的前脉冲抑制破坏。虽然丙戊酸盐和卡马西平对地佐环平（0.3毫克/千克，皮下注射）诱导的前脉冲抑制破坏没有影响，但碳酸锂加剧了地佐环平诱导的破坏。这些结果表明，丙戊酸盐、卡马西平和碳酸锂通过多巴胺能系统逆转前脉冲抑制的破坏。
