Delayed regional metabolic actions of phencyclidine.
Phencyclidine (PCP), a psychotomimetic drug of abuse, produces mental changes and manifestations in humans which are reminiscent of schizophrenia, though the mechanism of these actions remains unknown. We report here a biphasic time course of PCP action on regional cerebral glucose metabolism extending over 48 h. A single dose of PCP (8.6 mg/kg) produces an initial increase in glucose metabolism (at 3 h) and a later decrease in glucose metabolism (at 24 h) without a return to baseline until 48 h. A single lower dose of PCP (0.86 mg/kg), a dose which is considered selective for action at the NMDA-PCP receptor, produces no early metabolic change (at 3 h), but replicates the regional hypometabolism albeit less intense at 24 h. The delayed cerebral hypometabolism does not appear to be related to PCP-induced intracellular vacuolization, seen in the retrosplenial cortex. These metabolic changes may be associated with the psychotomimetic effects of PCP and thus may be relevant to psychosis in humans.
Gao
X M
XM
Maryland Psychiatric Research Center, Baltimore 21228.
Shirakawa
O
O
Du
F
F
Tamminga
C A
CA
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000473:pathology; D006651:Histocytochemistry; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005947:Glucose; D010622:Phencyclidine