Kazi Jamil Ahsan, Gee Chen Fun
Department of Anaesthesia, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
J Mol Neurosci. 2007;32(1):47-52. doi: 10.1007/s12031-007-0007-6.
The neuro-anatomical sites and molecular mechanism of action of gabapentin (GBP)-morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not known. Therefore, we examined the combined effects of GBP-Morphine on acute morphine induced c-Fos expression in rat striatum. The combined effect of GBP-Morphine was examined by means of c-Fos immunohistochemistry. A single intraperitoneal injection (i.p.) of morphine (10 mg/kg), saline (control), co-injection of GBP (150 mg/kg) with morphine (10 mg/kg) was administered under anaesthesia. Ninety minutes after drugs administration the deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde. Serial 40 mum thick sections of brain were cut and processed by immunohistochemistry to locate and quantify the sites and number of neurons with c-Fos immunoreactivity. Detection of c-Fos protein was performed using the peroxidase-antiperoxidase (PAP) detection protocol. Our present study demonstrated that, administration of GBP (150 mg/kg, i.p.) in combination with morphine (10 mg/kg, i.p.) significantly (p < 0.01) attenuated the acute morphine (10 mg/kg, i.p.) induced c-Fos expression in the rat striatum. Present results showed that GBP-morphine combination action prevented the acute morphine induced c-Fos expression in rat striatum. Moreover, this study provides first evidence of neuro-anatomical site and that GBP neutralized the morphine induced activation of rat striatum.
加巴喷丁（GBP）与吗啡相互作用以预防和逆转吗啡副作用以及增强吗啡镇痛效果的神经解剖学部位和分子作用机制尚不清楚。因此，我们研究了GBP与吗啡联合使用对大鼠纹状体中急性吗啡诱导的c-Fos表达的影响。通过c-Fos免疫组织化学检测GBP与吗啡的联合作用。在麻醉状态下，腹腔注射（i.p.）单次给予吗啡（10 mg/kg）、生理盐水（对照）、GBP（150 mg/kg）与吗啡（10 mg/kg）联合注射。给药90分钟后，将深度麻醉的大鼠经心脏灌注4%多聚甲醛。切取40μm厚的脑连续切片，通过免疫组织化学进行处理，以定位和定量具有c-Fos免疫反应性的神经元的部位和数量。使用过氧化物酶-抗过氧化物酶（PAP）检测方案检测c-Fos蛋白。我们目前的研究表明，GBP（150 mg/kg，腹腔注射）与吗啡（10 mg/kg，腹腔注射）联合给药显著（p<0.01）减弱了急性吗啡（10 mg/kg，腹腔注射）诱导的大鼠纹状体中c-Fos的表达。目前的结果表明，GBP与吗啡的联合作用可预防急性吗啡诱导的大鼠纹状体中c-Fos的表达。此外，本研究首次提供了神经解剖学部位的证据，表明GBP可中和吗啡诱导的大鼠纹状体激活。
