Wetzel Hanna N, Tsibulsky Vladimir L, Norman Andrew B
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0575, USA.
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0575, USA.
Drug Alcohol Depend. 2016 Nov 1;168:287-292. doi: 10.1016/j.drugalcdep.2016.09.024. Epub 2016 Oct 6.
Immunotherapy has shown potential as a treatment for cocaine abuse. The humanized recombinant anti-cocaine monoclonal antibody (mAb) with the preclinical designation h2E2 has been shown to decrease cocaine concentrations in the brain in rats, but its effects on cocaine self-administration behavior have never been tested.
The amount of cocaine needed to reinstate self-administration behavior (priming threshold) was calculated and the inter-injection intervals at unit doses of 0.3μmol/kg and 3μmol/kg during maintained self-administration were measured over a five-week baseline period. Rats trained to self-administer cocaine were infused with two doses of h2E2 (120mg/kg i.v.) 35days apart. Priming threshold and inter-injection intervals were measured for 35days after both injections.
After both injections of h2E2, priming thresholds were significantly increased (3-fold) compared to expected baseline and then gradually declined over 35days. A significant decrease (15-33%) in inter-injection intervals during maintained self-administration was also observed following both h2E2 infusions at the lower dose, and after the first injection at the higher dose. No significant decreases in body weight were observed after either injection, indicating a lack of toxicity following a second injection.
These data predict that the safety and effectiveness of h2E2 will be maintained after multiple treatments of this potential immunotherapy for cocaine abuse.
免疫疗法已显示出作为治疗可卡因滥用的潜力。临床前命名为h2E2的人源化重组抗可卡因单克隆抗体（mAb）已被证明可降低大鼠大脑中的可卡因浓度，但其对可卡因自我给药行为的影响从未得到测试。
计算恢复自我给药行为所需的可卡因量（启动阈值），并在为期五周的基线期内测量维持自我给药期间单位剂量为0.3μmol/kg和3μmol/kg时的注射间隔。对训练为自我给药可卡因的大鼠每隔35天静脉注射两剂h2E2（120mg/kg）。在两次注射后35天测量启动阈值和注射间隔。
两次注射h2E2后，启动阈值与预期基线相比显著增加（3倍），然后在35天内逐渐下降。在较低剂量的h2E2输注后以及较高剂量的第一次注射后，维持自我给药期间的注射间隔也显著缩短（15 - 33%）。两次注射后均未观察到体重显著下降，表明第二次注射后没有毒性。
这些数据预测，在对这种潜在的可卡因滥用免疫疗法进行多次治疗后，h2E2的安全性和有效性将得以维持。
