CHANGES IN [H-3] PK 11195 AND [H-3] 8-OH-DPAT BINDING FOLLOWING FOREBRAIN ISCHEMIA IN THE GERBIL

1 A high density of [H-3]-PK 11195 binding sites was present in gerbil cortical membranes (B(max) [H-3]-PK 11195 1360 +/- 71 fmol mg-1 prote in) in comparison to rat cortical membranes (254 +/- 21 fmol mg-1 prot ein). This effect was species-specific as similar findings were obtain ed with hippocampal membranes (B(max) 1430 +/- 111 fmol mg-1 protein i n gerbil, compared to 196 +/- 31 in rat). 2 RO 5-4864, also a peripher al type benzodiazepine compound, displayed low affinity for the [H-3]- PK 11195 site in the gerbil (pK(i) 6.57 +/- 0.02 and 6.70 +/- 0.12 in hippocampus and cortex respectively) compared to, rat (pK(i) 8.16 +/- 0.07 and 8.48 +/- 0.02). Central benzodiazepine compounds, diazepam an d flunitrazepam, also displayed this trend. 3 RO 5-4864 displaced [H-3 ]-PK 11195 binding from gerbil and rat cortical membranes through a co mpetitive interaction with Hill slopes close to unity. In both tissues , saturation isotherms of [H-3]-PK 11195 binding indicated that the pr esence of RO 5-4864 caused changes in K(d) without any effect on B(max ). In kinetic experiments, the presence of RO 5-4864 failed to modify the rate of dissociation of [H-3]-PK 11195 from equilibrium in both ra t and gerbil cortical membranes. 4 Forebrain ischaemia in the Mongolia n gerbil (5 min bilateral carotid artery occlusion) with 7 days recove ry caused a significant (P < 0.05) decrease in the density of hippocam pal 5-HT1A binding sites labelled by [H-3]-8-OH-DPAT (B(max) control, 393 +/- 33 fmol mg-1 protein; ischaemic, 289 +/- 21 fmol mg-1 protein) and an increase (P < 0.01) in [H-3]-PK 11195 binding sites (B(max) co ntrol, 1430 +/- 111 fmol mg-1 protein; ischaemic, 2160 +/- 170 fmol mg -1 protein). Ischaemia and recovery had no effect on the affinity of e ither ligand. 5 Autoradiography experiments in gerbil brain sections r evealed that the ischaemia-induced increase in [H-3]-PK 11195 binding was consistent and significant in the CA1 subfield on the hippocampus (control, 152 +/- 42 fmol mg-1 tissue; ischaemic, 314 +/- 43 fmol mg-1 tissue).