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.
Davidson
Colin
C
Psychiatry, Box 3870, Duke University Medical Center, NC 27710, United States. colda@duke.edu
Gopalan
Rupa
R
Ahn
Cassandra
C
Chen
Qiang
Q
Mannelli
Paolo
P
Patkar
Ashwin A
AA
Weese
G Daniel
GD
Lee
Tong H
TH
Ellinwood
Everett H
EH
D000818:Animals; D004359:Drug Therapy, Combination; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D017294:Ondansetron / Q000008:administration & dosage*; D010479:Pergolide / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D010479:Pergolide; D008694:Methamphetamine; D017294:Ondansetron