Group II mGlu receptor agonists inhibit behavioural and electrophysiological effects of DOI in mice.

It has been suggested that metabotropic glutamate (mGlu) receptor agonists selective for Group II mGlu receptors may have antipsychotic action. Therefore, we studied whether the effects, which could be related to psychotomimetic action of hallucinogenic drugs, are inhibited by Group II mGlu receptor agonists. The selective mGlu2/3 agonists LY354740 and LY379268 inhibited (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitches in mice in a dose-dependent manner. Furthermore, LY379268 suppressed an increase in the frequency of spontaneous excitatory synaptic potentials induced by bath-applied DOI in layer V pyramidal cells recorded in the murine medial frontal cortex. The data indicate that Group II mGlu receptor agonists may counteract the effects of hallucinogenic drugs.