Abstract
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.
Highlights
(+)-Methamphetamine (METH) addiction is a major public health problem throughout the world [1,2,3]
Spontaneous withdrawal from a chronic METH infusion elevated intracranial self-stimulation (ICSS) thresholds, and this effect was reversed by acute METH (Fig. 2A)
This effect was blocked by acute METH (Fig. 2A), as thresholds in the METH + METH group did not differ from the SAL + SAL group and were significantly lower than thresholds in the METH + SAL group (t (75) = 7.0, p < 0.001)
Summary
The goal of this study was to examine whether mAb7F9 could attenuate the effects of acute METH on ICSS in rats
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