Kofman O, Patishi Y
Department of Behavioral Sciences, Faculty of Social Sciences and Humanities, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Eur Neuropsychopharmacol. 1999 Sep;9(5):385-97. doi: 10.1016/s0924-977x(99)00009-7.
The therapeutic mechanism of the action of lithium in the treatment of bipolar affective disorder is not known, in spite of a burgeoning number of biochemical studies linking lithium to signal transduction processes. This article reviews a decade of studies examining the behavioural manifestations of manipulating inositol, cyclic adenosine monophosphate (cAMP) and G proteins in rats. Inositol, forskolin, dibutyryl cAMP and pertussis toxin all interacted with lithium when rearing behavior was measured. Lithium potentiated the increase in locomotion induced by injections of cholera toxin into the nucleus accumbens, consistent with the hypothesis that it inactivates inhibitory G proteins. More specific interactions were found between lithium and inositol following cholinergic and serotonergic stimulation. Inositol, but not forskolin, attenuated lithium-pilocarpine seizures and the enhancement of the serotonin syndrome; however, inositol had no effect on lithium-induced attenuation of wet dog shakes following an injection of 5-hydroxytryptophan. Behavioural evidence supports biochemical findings suggesting that lithium's interactions with the phoshphatidyl inositol and cyclic AMP signal transduction systems may be relevant to its therapeutic effects in bipolar disorder. Further research on more specific behaviours may elucidate the relevant pharmacological mechanisms underlying the therapeutic effect of lithium.
尽管将锂与信号转导过程联系起来的生化研究数量不断增加，但锂在治疗双相情感障碍中的作用机制仍不清楚。本文回顾了十年来在大鼠中研究操纵肌醇、环磷酸腺苷（cAMP）和G蛋白的行为表现的研究。当测量饲养行为时，肌醇、福斯高林、二丁酰环磷腺苷和百日咳毒素都与锂相互作用。锂增强了向伏隔核注射霍乱毒素所诱导的运动增加，这与它使抑制性G蛋白失活的假设一致。在胆碱能和5-羟色胺能刺激后，发现锂与肌醇之间有更具体的相互作用。肌醇而非福斯高林减轻了锂-毛果芸香碱癫痫发作和血清素综合征的增强；然而，肌醇对注射5-羟色氨酸后锂诱导的湿狗样抖动减弱没有影响。行为学证据支持生化研究结果，表明锂与磷脂酰肌醇和环磷腺苷信号转导系统的相互作用可能与其在双相情感障碍中的治疗作用相关。对更具体行为的进一步研究可能会阐明锂治疗作用背后的相关药理机制。
