title: Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex.
abstract: The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5-HT(2A) antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT(2A/C) agonist [-]-2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 microM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.
authors.affiliation: Department of Psychology, University at Buffalo, The State University of New York, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Muschamp
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: Regina
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hull
authors.forename: Jerrold C
authors.initials: JC
authors.lastname: Winter
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rabin
mesh_terms: D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology*; D000818:Animals; D045604:Extracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000096:biosynthesis / Q000378:metabolism*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D018698:Glutamic Acid; D008238:Lysergic Acid Diethylamide