Effects of phencyclidine on gamma-aminobutyric acid receptors in the mouse

The interaction of PCP with the GABAergic system in the brain of the mouse has been investigated. Male ICR mice were rendered tolerant by five days of injections with PCP, 40 mg/kg, i.p., once daily. The control group received saline, 0.1 ml/10 g, i.p., once daily for five days. On the sixth day, the whole brain was removed and the synaptic membrane was isolated. After 18 hours in the freezer at -80°C, half of the synaptic membrane was treated with 0.05% Triton X-100 to remove the endogenous inhibitor. A GABA binding assay for the high affinity receptor bindings was then performed and comparisons were made between the control and the PCP- tolerant groups. In both of the preparations, synaptic and Triton X-100 treated membranes, the specific binding of GABA was significantly greater for the PCP-tolerant group. It was also shown that the CD₅₀, induction of clonic and tonic convulsions, of pentylenetetrazol was not changed in the PCP-tolerant animal. However, there was a significant decrease in the CD₅₀ of bicuculline (from 6.8 mg/kg to 3.7 mg/kg) in PCP-tolerant animals. From the data presented, an alteration of the GABAergic system apparently occurs in the mouse which is rendered tolerant to PCP.