THE EFFECT OF PHENCYCLIDINE ON [H-3] GABA AND [H-3] FLUNITRAZEPAM BINDING IN THE BRAIN OF NAIVE AND HANDLING-HABITUATED RATS

The effects of handling and handling combined with phencyclidine (PCP) treatment on GABAergic neurotransmission were studied in Sprague-Dawley rats. The animal material consisted of handling-habituated (HH, for 11 d), acutely handled (naive, N), handling-habituated and PCP-treated (10 mg kg(-1) i.p., HH + PCP) and acutely handled (naive) PCP-treated (N + PCP) and unhandled 'control' rats. The binding of [H-3]GABA and [H-3]flunitrazepam (FLU) was studied with membranes and the release of [H-3]GABA with slices prepared from the striatum and frontal cortex. In the striatum the maximal binding capacity (B-max) and the binding constant (K-D) of [H-3]GABA were the same in N and HH rats, but in the frontal cortex K-D was lower in N rats. K-D constants of [H-3]FLU were significantly lower in both brain areas in N rats than in HH rats. After PCP treatment both B-max and K-D for [H-3]FLU increased in these two brain areas in handling-habituated rats, whereas B-max of [H-3]GABA diminished. Neither handling nor PCP had any effect on [H-3]GABA release from striatal and frontal cortical slices. Handling prior to killing thus affects differently the GABAergic parameters studied and modulates the PCP-induced effects.