Reduction in methamphetamine induced sensitization and reinstatement after combined pergolide plus ondansetron treatment during withdrawal

We have previously found the 5-HT3 receptor antagonist ondansetron to be useful in reducing cocaine self-administration and cocaine induced sensitization in rats when given during cocaine withdrawal. More recently we have found the combination of the dopamine agonist pergolide plus ondansetron, 3.5 h later, to reverse cocaine sensitization and associated changes in NMDA and AMPA receptors. Here we tested this drug combination in 1) a methamphetamine sensitization model and 2) a reinstatement model after intravenous methamphetamine self-administration using a nose-poke task. We found pergolide plus ondansetron given from days 3–7 of methamphetamine withdrawal to reverse methamphetamine induced sensitization and attenuate reinstatement. We hypothesize that pergolide may evoke a methamphetamine associated memory and that ondansetron can disrupt its reconsolidation. These data suggest that pergolide plus ondansetron treatment may be useful as a therapy to reduce relapse in methamphetamine abusers.