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-HT(2A) 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-HT(2A) receptors induce head shakes when directly administered into the medial prefrontal cortex. The purpose of the present experiments was to examine whether an interaction occurs between mGlu2/3 and 5-HT(2A) receptors on a behavioral level using head shakes induced by phenethylamine hallucinogens as a model of 5-HT(2A) 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 LY341495 (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 may be mediated in part, via increased glutamate release following activation of 5-HT(2A) receptors.
Gewirtz
J C
JC
Department of Psychiatry, Yale School of Medicine, Connecticut Mental Health Center, and the Ribicoff Research Facilities, Rm. 335d, 34 Park Street, New Haven, CT 06508, USA.
Marek
G J
GJ
D000596:Amino Acids / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D000662:Amphetamines; D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; C114624:LY 341495; D044402:Receptor, Serotonin, 5-HT2A; D018094:Receptors, Metabotropic Glutamate; D011985:Receptors, Serotonin; D014966:Xanthenes; C104753:eglumetad; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine