The anti-(+)-methamphetamine monoclonal antibody mAb7F9 attenuates acute (+)-methamphetamine effects on intracranial self-stimulation in rats.
Passive immunization with monoclonal antibodies (mAbs) against (+)-methamphetamine (METH) is being evaluated for the treatment of METH addiction. A human/mouse chimeric form of the murine anti-METH mAb7F9 has entered clinical trials. This study examined the effects of murine mAb7F9 on certain addiction-related behavioral effects of METH in rats as measured using intracranial self-stimulation (ICSS). Initial studies indicated that acute METH (0.1-0.56 mg/kg, s.c.) lowered the minimal (threshold) stimulation intensity that maintained ICSS. METH (0.3 mg/kg, s.c.) also blocked elevations in ICSS thresholds (anhedonia-like behavior) during spontaneous withdrawal from a chronic METH infusion (10 mg/kg/day x 7 days). In studies examining effects of i.v. pretreatment with mAb7F9 (at 30, 100, or 200 mg/kg), 200 mg/kg blocked the ability of an initial injection of METH (0.3 mg/kg, s.c.) to reduce baseline ICSS thresholds, but was less capable of attenuating the effect of subsequent daily injections of METH. MAb7F9 (200 mg/kg) also produced a small but significant reduction in the ability of METH (0.3 mg/kg, s.c.) to reverse METH withdrawal-induced elevations in ICSS thresholds. These studies demonstrate that mAb7F9 can partially attenuate some addiction-related effects of acute METH in an ICSS model, and provide some support for the therapeutic potential of mAb7F9 for the treatment of METH addiction.
Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America; Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Andrew C
AC
Harris
Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America; Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Mark G
MG
LeSage
Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America.
David
D
Shelley
Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America.
Jennifer L
JL
Perry
Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America; Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Paul R
PR
Pentel
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
S Michael
SM
Owens
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016739:Behavior, Addictive / Q000276:immunology; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D007116:Immunization, Passive; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation
D000911:Antibodies, Monoclonal; D008694:Methamphetamine