Psychosis: pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia?
Non-competitive NMDA receptor antagonists, such as phencyclidine, ketamine and MK801, produce psychosis in humans. These drugs also produce injury to cingulate-retrosplenial cortex in adult rodents that can be prevented by GABA-receptor agonists and antipsychotics such as haloperidol and clozapine. MK801 injections into anterior thalamus reproduce limbic cortex injury, and GABA-receptor agonist injections into anterior thalamus prevent injury produced by systemic MK801. Inhibition of NMDA receptors on GABAergic thalamic reticular nucleus neurons might activate thalamocortical 'injury' circuits in animals. Pathological activation of thalamocortical circuits might also mediate the psychosis produced by NMDA-receptor antagonists in humans, and might contribute to psychosis in schizophrenia.
Sharp
F R
FR
Department of Neurology and Neurosciences Program, University of Cincinnati Vontz Center, 3125 Eden Avenue Rm 2327, Cincinnati, OH 45267-0536, USA. frank.sharp@uc.edu
Tomitaka
M
M
Bernaudin
M
M
Tomitaka
S
S
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D006801:Humans; D008032:Limbic System / Q000187:drug effects*; D008959:Models, Neurological; D011605:Psychoses, Substance-Induced / Q000209:etiology* / Q000473:pathology; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012559:Schizophrenia / Q000473:pathology; D013788:Thalamus / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate