Lysergic acid diethylamide and [−]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex

• Published in: Brain research Vol. 1023; no. 1; pp. 134 - 140
• Main Authors: Muschamp, John W., Regina, Meredith J., Hull, Elaine M., Winter, Jerrold C., Rabin, Richard A.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 08.10.2004; Amsterdam Elsevier; New York, NY
• Subjects: 5-HT 2A receptor; Animals; Biological and medical sciences; DOM; DOM 2,5-Dimethoxy-4-Methylamphetamine - pharmacology; Drug addictions; Extracellular Fluid - drug effects; Extracellular Fluid - metabolism; Glutamate; Glutamic Acid - biosynthesis; Glutamic Acid - metabolism; Hallucinogen; In vivo microdialysis; LSD; Lysergic Acid Diethylamide - pharmacology; Male; Medical sciences; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Rats; Rats, Inbred F344; Receptor, Serotonin, 5-HT2A - metabolism; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Toxicology; DOM; 5-HT 2A receptor; Hallucinogen; Prefrontal cortex; Neural basis of behavior; In vivo microdialysis; Glutamate; LSD; 5-HT2A serotonin receptor; Rat; Rodentia; Central nervous system; Metamfetamine; Lysergide; Extracellular; Encephalon; Vertebrata; 5-HT2A receptor; Mammalia; Microdialysis; Animal; Excitatory aminoacid; Neurotransmitter
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.07.044

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 μM) 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.