Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food

Abstract

(+)-Methamphetamine (METH) addiction is a chronic disease that interferes with fundamental brain-mediated behaviors and biological functions like eating. These studies present preclinical efficacy and safety profiles for a METH conjugate vaccine (ICKLH-SMO9) designed to treat METH abuse. ICKLH-SMO9 efficacy and safety were assessed over a 16-week period by monitoring general health and stability of responding in a food maintained behavioral paradigm. Male Sprague–Dawley rats were trained to lever press for food reinforcers until stable behavior was established. Rats (n=9/group) were then immunized with 100μg of a control antigenic carrier protein (ICKLH-Cys) or ICKLH-SMO9 in Alhydrogel® adjuvant, with booster immunizations at 4, 8 and 12weeks. Health, immunization site and behavior were assessed daily. No adverse effects were found. During weeks 14–16, when antibody titers and METH affinity (Kd=13.9±1.7nM) were maximal, all rats received progressively higher METH doses (0.3–3.0mg/kg) every 3–4days, followed by behavioral testing. Even though the lower METH doses from 0.3 to 1.0mg/kg produced no impairment in food maintained behavior, 3.0-mg/kg in control rats showed significantly (p<0.05) reduced response rates and number of reinforcers earned, as well as reduced food intake. In sharp contrast, the ICKLH-SMO9 group showed no changes in food maintained behavior at any METH dose, even though METH serum concentrations showed profound increases due to anti-METH antibody binding. These findings suggest the ICKLH-SMO9 vaccine is effective and safe at reducing adverse METH-induced effects, even at high METH doses.