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 glutamatergic neurotransmission were studied in mice. The binding of tritiated N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) to cerebral cortical membranes and the uptake of [H-3]glutamate by cortical synaptosomal preparations were assessed after PCP treatment (1 mg/d/mouse for 3 days) with implanted minipumps. The binding capacity B(max) of TCP significantly increased but the binding constant K(D) remained the same after PCP exposure, indicating that more binding sites became available. The basic properties of the binding remained unaltered but the actions of glutamate, glutamate receptor agonists and glycine were potentiated in PCP-treated mice. The uptake of glutamate was saturable, consisting of both high- and low-affinity transport components. After PCP exposure the transport constant K(m) of the high-affinity component increased and that of the low-affinity component was not changed. The maximal velocity V of the high-affinity component increased while that of the low-affinity transport decreased. Moreover, inhibition by structural analogues was potentiated, suggesting modification of the glutamate transporter. The results show that chronic PCP treatment, used as a model of psychosis, markedly affects the studied glutamatergic parameters.