Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors

Recent electrophysiological studies in our laboratory have demonstrated a physiological interaction between 5-HT2A and metabotropic glutamate2/3 (mGlu2/3) receptors in the medial prefrontal cortex. Several behavioral studies have found that phenethylamine hallucinogens with partial agonist activity at 5-HT2A receptors induce head shakes when directly administered into Me medial prefrontal cortex. The purpose of Me present experiments was to examine whether an interaction occurs between mGlu2/3 and 5-HT2A receptors on a behavioral level using head shakes induced by phenethylamine hallucinogens as a model of 5-HT2A receptor activation. Administration of the mGlu2/3 agonist LY354740 (0.3-10 mg/kg, ip) suppressed head shakes induced by the phenethylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Conversely, administration of the mGlu2/3 antagonist LY342495 (1 mg/kg, ip) enhanced the frequency of DOI-induced head shakes. Taken together, these results raise the possibility that the psychomimetic properties of hallucinogenic drugs maybe mediated in part, via increased glutamate release following activation of 5-HT2A receptors. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.