Calcium-dependent GABA release from mouse brain slices following acute and chronic phencyclidine administration

Calcium dependent release of preloaded [³H]-γ-aminobutyric acid (GABA) from mouse striatal and cerebellar slices was investigated after acute and chronic administration of phencyclidine (PCP). Chronic administration of PCP was achieved by osmotic minipumps which delivered PCP at a constant rate. Ca⁺⁺ dependent GABA release from the cerebellum but not from the striatum of naive mouse was significantly inhibited by the in vitro addition of 1 x 10^-4 M PCP. Acute administration of low doses (10 mg/kg) of PCP enhanced CA⁺⁺ dependent GABA release from the striatum, whereas in high doses (40 mg/kg) a decrease in release was observed. A similar general trend of response was observed when cerebellar slices were used. Continuous administration of PCP (1 mg/kg for 2 days) by osmotic minipump implantation decreased GABA release from striatal slices; the GABA release, however, returned to control levels after 4 and 6 days of continuous administration. On the other hand, cerebellar GABA release was inhibited only in the 4-day treated group. The spontaneous GABA release was not affected by any of the PCP treatments except in the acutely treated striatal slices. These results implicate an involvement of the GABA system in the CNS effects of PCP including tolerance development