Pharmacology & toxicology
January 1, 1999
G Ellison, A Keys, K Noguchi
Continuous administration of phencyclidine (PCP) to rats over several days causes neural degeneration in limbic brain structures such as the retrosplenial cortex, hippocampus, and piriform cortex. Twenty-one days after the same dosing regimen, autoradiography revealed enduring changes in several receptor types—including decreased binding of TCP, flunitrazepam, and mazindol—in many limbic regions where degeneration had been reported. Unexpectedly, some long-term receptor alterations appeared in structures without immediate signs of degeneration, like the anterior cingulate cortex and caudate nucleus, and some changes developed gradually after drug cessation. These findings do not point to a single source for the neurotoxicity and may inform models of schizophrenia.
Brain research. Brain research reviews
February 1, 1995
G Ellison
Phencyclidine (PCP) and ketamine can induce a model psychosis that mimics schizophrenic symptoms including flattened affect, dissociative thought disorder, depersonalization, and catatonic states, with chronic users showing persisting memory deficits. Dizocilpine (MK-801) shares with PCP and ketamine the property of blocking the NMDA ion-channel in a non-competitive manner. Animal studies show these drugs cause neurotoxic effects on neurons in the posterior cingulate cortex and, when given continuously for several days, induce neuronal degeneration in other limbic structures including the piriform cortex, entorhinal cortex, and dentate gyrus.
Neuroreport
October 25, 1993
G Ellison, R C Switzer
Different drugs of abuse that can produce psychosis in chronic users cause distinct patterns of brain damage. Continuous administration of D-amphetamine or cocaine over five days led to pronounced degeneration in the fasciculus retroflexus, a brain fiber bundle, while D-amphetamine also damaged the striatum. Phencyclidine (PCP) caused damage largely confined to the posterior entorhinal cortex, ventral dentate gyrus, and cingulate cortex. Methamphetamine, given in a high-dose but shorter regimen, caused widespread degeneration including in the striatum. These distinct patterns suggest two different anatomical locations may be involved in psychosis: the fasciculus retroflexus and the ventral parahippocampus and hippocampus.