Tomasiewicz Hilarie C, Mague Stephen D, Cohen Bruce M, Carlezon William A
Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, MRC 217 115 Mill St., Belmont, MA 02478, USA.
Brain Res. 2006 Jun 6;1093(1):83-94. doi: 10.1016/j.brainres.2006.03.102. Epub 2006 May 9.
Lithium and valproic acid are mood-stabilizing agents that are often used to manage the episodes of mania and depression that characterize bipolar disorder. These agents develop clinical efficacy with chronic treatment, but the neurobiological actions that contribute to their therapeutic effects remain unclear. The present work was designed to study and compare various behavioral effects of short-term administration of lithium chloride (LiCl) and valproic acid (VPA) in rats. Specifically, we examined the effects of acute and sub-acute injections of these agents on locomotor activity, behavior in the forced swim test (FST), and intracranial self-stimulation (ICSS) thresholds. Locomotor activity studies were used to identify the range of doses with gross behavioral effects in rats. At doses below those that suppressed activity (total distance traveled, in cm) in 1-h test sessions, LiCl had prodepressant-like effects: it increased immobility in the FST, an effect opposite to that typically seen with standard antidepressants, and it increased ICSS thresholds, an effect similar to that typically seen during withdrawal from drugs of abuse. In contrast, VPA had no effects in the FST or on ICSS thresholds. This work identifies potentially important characteristics that distinguish the drugs at doses below those that produce non-specific behavioral effects, and thus serves as a basis for designing and interpreting studies of long-term treatment.
锂盐和丙戊酸是心境稳定剂，常用于治疗双相情感障碍所特有的躁狂和抑郁发作。这些药物通过长期治疗产生临床疗效，但其治疗作用所涉及的神经生物学机制仍不清楚。本研究旨在探讨和比较短期给予大鼠氯化锂（LiCl）和丙戊酸（VPA）后的各种行为效应。具体而言，我们检测了急性和亚急性注射这些药物对大鼠自发活动、强迫游泳试验（FST）行为以及颅内自我刺激（ICSS）阈值的影响。自发活动研究用于确定对大鼠产生明显行为效应的剂量范围。在低于1小时试验期内抑制活动（总移动距离，单位为厘米）的剂量下，LiCl具有类似促抑郁的作用：它增加了FST中的不动时间，这一效应与标准抗抑郁药通常所见的效应相反，并且它提高了ICSS阈值，这一效应与滥用药物戒断期间通常所见的效应相似。相比之下，VPA对FST或ICSS阈值没有影响。这项研究确定了在产生非特异性行为效应的剂量以下区分这两种药物的潜在重要特征，从而为设计和解释长期治疗研究奠定了基础。
