title: Persisting changes in brain glucose uptake following neurotoxic doses of phencyclidine which mirror the acute effects of the drug.
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.
authors.affiliation: Department of Psychology, UCLA 90024, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Ellison
authors.forename: A S
authors.initials: AS
authors.lastname: Keys
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006213:Hallucinogens / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006213:Hallucinogens; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005947:Glucose; D010622:Phencyclidine