PERSISTING CHANGES IN BRAIN GLUCOSE-UPTAKE FOLLOWING NEUROTOXIC DOSESOF PHENCYCLIDINE WHICH MIRROR THE ACUTE EFFECTS OF THE DRUG

Phencyclidine (PCP) can induce a model psychosis which has a number of similarities to dementias and schizophrenia. In some cases the psycho sis persists for prolonged periods after drug discontinuation. N-Methy l-D-aspartate (NMDA) antagonists such as PCP induce increases in gluco se metabolism in a variety of brain structures but most notably in lim bic regions such as retrosplenial, piriform, and entorhinal cortex, hi ppocampus, and olfactory tubercle. When given continuously for several days, these NMDA antagonists induced neural degeneration in these sam e critical limbic areas. In the present study regional 2-fluorodeoxygl ucose (FDG) uptake was measured in rats at both 24 h and 10 days after neurotoxic, 5-day ''binge'' PCP administration. At 24 h after minipum p removal there were persisting and large increases in glucose uptake in many brain regions, with maximal changes in the same limbic structu res in which neurotoxicity has been observed. Surprisingly, many of th ese re ions still showed elevated glucose metabolism after 10 days of recovery. These findings suggest an anatomical and neurochemical subst rate for the persisting psychosis which can occur following PCP.