Hayase T, Yamamoto Y, Yamamoto K
Department of Legal Medicine, Kyoto University Graduate School of Medicine, Faculty of Medicine, Kyoto 606-8501, Japan.
Nihon Arukoru Yakubutsu Igakkai Zasshi. 2000 Dec;35(6):402-14.
The present study evaluated the effects of mixed opioid drugs on the severity of cocaine (COCA) toxicity by examining stress-related behavioral alterations in mice. In order to ascertain the strength of the stress, the continuous observation of the behavioral symptoms in the cage and the forced swimming test (Porsolt test) were performed in the COCA (75 mg/kg, i.p.)-treated groups, with or without the mixed mu-kappa receptor-related opioid drugs, buprenorphine (BUP) and pentazocine (PEN). Using the high-sensitivity activity measuring instrument Supermex, both the spontaneous behaviors in the cage and the forced swimming behaviors in the water were assessed as activity counts. The behavioral alterations in the COCA-treated groups were compared with a group of mice given a 10 min immobilization stress (IM group). In the COCA-only group, a prolonged increase in the spontaneous behaviors accompanied by convulsive seizures was observed even in the surviving mice, unlike in the IM group. However, an acceleration of behavioral despair in the Porsolt test similar to that observed in the IM group was observed in the COCA group after the disappearance of the acute toxic symptoms (5 hours after the COCA treatment). Among the opioid-treated groups, the mortality rate was attenuated only in the COCA-BUP (0.25 mg/kg, i.p.) group. In the COCA-BUP group, a prolonged suppression of the morbid hyperactivity in the cage except for the convulsive seizures, and a normalization of the swimming behavior in the Porsolt test were observed in the survivors. On the other hand, in the COCA-PEN (5 mg/kg, i.p.) group, the swimming behavior in the Porsolt test was abnormally increased in addition to the prolonged morbid hyperactivity in the cage. Therefore, the COCA-induced stress-related behaviors were normalized in the group of mice treated with BUP, a group with a good prognosis.
本研究通过检测小鼠应激相关行为改变，评估了混合阿片类药物对可卡因（COCA）中毒严重程度的影响。为确定应激强度，在接受COCA（75mg/kg，腹腔注射）治疗的组中，无论是否使用与μ-κ受体相关的混合阿片类药物丁丙诺啡（BUP）和喷他佐辛（PEN），均进行了笼内行为症状的持续观察和强迫游泳试验（Porsolt试验）。使用高灵敏度活动测量仪器Supermex，将笼内自发行为和水中强迫游泳行为评估为活动计数。将COCA治疗组的行为改变与一组接受10分钟固定应激的小鼠（IM组）进行比较。在仅使用COCA的组中，即使在存活小鼠中也观察到自发行为的持续增加并伴有惊厥发作，这与IM组不同。然而，在急性毒性症状消失后（COCA治疗后5小时），COCA组在Porsolt试验中观察到与IM组相似的行为绝望加速。在阿片类药物治疗组中，仅COCA-BUP（0.25mg/kg，腹腔注射）组的死亡率降低。在COCA-BUP组中，存活小鼠除惊厥发作外，笼内病态多动得到持续抑制，且Porsolt试验中的游泳行为恢复正常。另一方面，在COCA-PEN（5mg/kg，腹腔注射）组中，除笼内病态多动持续外，Porsolt试验中的游泳行为异常增加。因此，用BUP治疗的小鼠组中，COCA诱导的应激相关行为恢复正常，该组预后良好。
