Persisting changes in brain glucose uptake following neurotoxic doses of phencyclidine which mirror the acute effects of the drug.

Phencyclidine (PCP) can cause a psychosis resembling schizophrenia and dementia that sometimes persists long after the drug is stopped. In rats, a five-day continuous 'binge' of PCP caused lasting increases in brain glucose metabolism, especially in limbic regions (retrosplenial, piriform, and entorhinal cortex, hippocampus, and olfactory tubercle). These increases were still present 10 days after the drug was removed, indicating that the metabolic changes persist. The findings suggest a brain basis for the prolonged psychosis that can follow PCP use.

Study at a glance

Abstract

Phencyclidine (PCP) can induce a model psychosis which has a number of similarities to dementias and schizophrenia. In some cases the psychosis persists for prolonged periods after drug discontinuation. N-Methyl-D-aspartate (NMDA) antagonists such as PCP induce increases in glucose metabolism in a variety of brain structures but most notably in limbic regions such as retrosplenial, piriform, and entorhinal cortex, hippocampus, and olfactory tubercle. When given continuously for several days, these NMDA antagonists induced neural degeneration in these same critical limbic areas. In the present study regional 2-fluorodeoxyglucose (FDG) uptake was measured in rats at both 24 h and 10 days after neurotoxic, 5-day "binge" PCP administration. At 24 h after minipump removal there were persisting and large increases in glucose uptake in many brain regions, with maximal changes in the same limbic structures in which neurotoxicity has been observed. Surprisingly, many of these regions still showed elevated glucose metabolism after 10 days of recovery. These findings suggest an anatomical and neurochemical substrate for the persisting psychosis which can occur following PCP.