Kosten Therese A, Shen Xiaoyun Y, Kinsey Berma M, Kosten Thomas R, Orson Frank M
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas; The Michael E DeBakey Veterans' Affairs Medical Center, Houston, Texas.
Am J Addict. 2014 Nov-Dec;23(6):604-7. doi: 10.1111/j.1521-0391.2014.12152.x. Epub 2014 Sep 22.
Immunotherapy for drug addiction is being investigated in several laboratories but most studies are conducted in animals of one sex. Yet, women show heightened immune responses and are more likely to develop autoimmune diseases than men. The purpose of this study was to compare the effects of an active anti-cocaine vaccine, succinyl-norcocaine conjugated to keyhole limpet hemocyanin, for its ability to elicit antibodies and alter cocaine-induced ambulatory activity in male versus female mice.
Male and female BALB/c mice were vaccinated (n = 44) or served as non-vaccinated controls (n = 34). Three weeks after initial vaccination, a booster was given. Ambulatory activity induced by cocaine (20 mg/kg) was assessed at 7 weeks and plasma obtained at 8 weeks to assess antibody levels.
High antibody titers were produced in mice of both sexes. The vaccine reduced ambulatory activity cocaine-induced but this effect was greater in female compared to male mice.
The efficacy of this anti-cocaine vaccine is demonstrated in mice of both sexes but its functional consequences are greater in females than males.
Results point to the importance of testing animals of both sexes in studies of immunotherapies for addiction.
多个实验室正在对药物成瘾的免疫疗法进行研究,但大多数研究仅在单一性别的动物中开展。然而,女性的免疫反应更为强烈,且比男性更易患自身免疫性疾病。本研究旨在比较一种活性抗可卡因疫苗(匙孔血蓝蛋白偶联琥珀酰去甲可卡因)在雄性和雌性小鼠中引发抗体的能力以及改变可卡因诱导的自主活动的效果。
将雄性和雌性BALB/c小鼠分为接种疫苗组(n = 44)和未接种疫苗的对照组(n = 34)。初次接种疫苗三周后进行加强免疫。在7周时评估可卡因(20 mg/kg)诱导的自主活动,并在8周时采集血浆以评估抗体水平。
两性小鼠均产生了高抗体滴度。该疫苗降低了可卡因诱导的自主活动,但与雄性小鼠相比,雌性小鼠的这种效果更为显著。
这种抗可卡因疫苗在两性小鼠中均显示出疗效,但其功能影响在雌性小鼠中比雄性小鼠更大。
研究结果表明在成瘾免疫疗法研究中对两性动物进行测试的重要性。