Group III mGlu receptor agonist, ACPT-I, attenuates morphine-withdrawal symptoms after peripheral administration in mice

Several lines of evidence implicate dysfunction of glutamatergic neurotransmission in opiate dependence and withdrawal. Functional antagonists of glutamatergic system, including compounds acting on both ionotropic and metabotropic glutamate receptors (group I mGlu receptor antagonists and group II mGlu receptor agonists), have been shown to decrease behavioural signs of opiate withdrawal in rodents. In the present study we analyzed an influence of group III mGlu receptor agonist, ACPT-I, on opioid withdrawal syndrom, induced by repeated morphine administration and final naloxone injection. We show, that ACPT-I significantly attenuated typical symptoms of naloxone-induced morphine withdrawal, after peripheral administration in C57BL/6J mice. These data indicate an important role of group III mGlu receptors in morphine withdrawal states and suggest that activation of group III mGlu receptors may reduce opiate withdrawal symptoms. (C) 2009 Elsevier Inc. All rights reserved.