PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent.
The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [14C]-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.
Tamminga
C A
CA
Experimental Therapeutics Branch, NINCDS, Bethesda, MD 20892.
Tanimoto
K
K
Kuo
S
S
Chase
T N
TN
Contreras
P C
PC
Rice
K C
KC
Jackson
A E
AE
O'Donohue
T L
TL
D000215:Acylation; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine
D002250:Carbon Radioisotopes; D003837:Deoxy Sugars; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; C044705:metaphit; D003847:Deoxyglucose; D010622:Phencyclidine