Lysergic acid diethylamide and [−]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex
John W. Muschamp, Meredith J. Regina, Elaine M. Hull, Jerrold C Winter, Richard A. Rabin
Brain Research August 27, 2004 DOI: 10.1016/j.brainres.2004.07.044 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | LSD DOM M100907 |
| Dose | 0.1 mg/kg LSD, 0.6 mg/kg DOM, 0.05 mg/kg M100907 |
| Topics | LSD Serotonin |
| Keywords | Microdialysis Hallucinogen Glutamate receptor Pharmacology Agonist Extracellular In vivo Prefrontal cortex Nmda receptor Biochemistry |
| Citations | 116 |
| Key findings | Hallucinogens LSD and DOM increase extracellular glutamate in the prefrontal cortex via 5-HT(2A) receptor activation. |
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.