PHENCYCLIDINE TREATMENT IN MICE - EFFECTS ON PHENCYCLIDINE BINDING-SITES AND GLUTAMATE UPTAKE IN CEREBRAL-CORTEX PREPARATIONS

The effects of a psychotomimetic drug, phencyclidine (PCP), on glutama tergic neurotransmission were studied in mice. The binding of tritiate d N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) to cerebral cortical mem branes and the uptake of [H-3]glutamate by cortical synaptosomal prepa rations were assessed after PCP treatment (1 mg/d/mouse for 3 days) wi th implanted minipumps. The binding capacity B(max) of TCP significant ly increased but the binding constant K(D) remained the same after PCP exposure, indicating that more binding sites became available. The ba sic properties of the binding remained unaltered but the actions of gl utamate, glutamate receptor agonists and glycine were potentiated in P CP-treated mice. The uptake of glutamate was saturable, consisting of both high- and low-affinity transport components. After PCP exposure t he transport constant K(m) of the high-affinity component increased an d that of the low-affinity component was not changed. The maximal velo city V of the high-affinity component increased while that of the low- affinity transport decreased. Moreover, inhibition by structural analo gues was potentiated, suggesting modification of the glutamate transpo rter. The results show that chronic PCP treatment, used as a model of psychosis, markedly affects the studied glutamatergic parameters.