Zohar Joseph, Matar Michael A, Ifergane Gal, Kaplan Zeev, Cohen Hagit
The Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv University, Israel.
Eur Neuropsychopharmacol. 2008 Sep;18(9):653-66. doi: 10.1016/j.euroneuro.2008.04.009. Epub 2008 Jun 5.
The short- and long-term behavioral effects of a brief course of pregabalin, an antiepileptic structural analogue of alpha-aminobyturic acid with analgesic and anxiolytic effects, were assessed in an animal model of post-traumatic stress disorder (PTSD).
Two-hundred thirty-three adult male Sprague-Dawley rats were employed. Behavioral responses to traumatic stress exposure (predator urine scent) were assessed immediately after (1 h) and 30 days after treatment with saline or pregabalin (at doses of 30, 100 and 300 mg/kg) in terms of behavior in the elevated plus maze (EPM) and the acoustic startle response (ASR) paradigms. At day 31 the freezing response to a trauma cue (clean cat litter) was assessed. The same treatment regimen initiated at day 7 was assessed at day 30 and in response to the trauma cue on day 31 in a separate experiment.
In the short term, doses of 100 mg/kg and 300 mg/kg of pregabalin effectively attenuated anxiety-like behaviors. In the longer-term, pregabalin did not attenuate the onset of PTSD-like behaviors or the prevalence rates of severe cue-responses, for either the immediate or the delayed treatment regimens.
Pregabalin may present an alternative compound for acute anxiolytic treatment after exposure to trauma, but has no long-term protective/preventive effects.
在创伤后应激障碍(PTSD)动物模型中,评估了抗癫痫药加巴喷丁(一种具有镇痛和抗焦虑作用的α-氨基丁酸结构类似物)短期和长期的行为效应。
使用233只成年雄性Sprague-Dawley大鼠。在给予生理盐水或加巴喷丁(剂量分别为30、100和300mg/kg)治疗后1小时及30天,根据高架十字迷宫(EPM)和听觉惊吓反应(ASR)范式中的行为,评估对创伤应激暴露(捕食者尿液气味)的行为反应。在第31天,评估对创伤线索(干净猫砂)的僵住反应。在另一项实验中,评估在第7天开始的相同治疗方案在第30天以及对第31天创伤线索的反应。
短期内,100mg/kg和300mg/kg剂量的加巴喷丁有效减轻了焦虑样行为。长期来看,对于即时或延迟治疗方案,加巴喷丁均未减轻PTSD样行为的发作或严重线索反应的发生率。
加巴喷丁可能是创伤暴露后急性抗焦虑治疗的替代化合物,但没有长期保护/预防作用。