Differential pharmacological properties of GABAA/benzodiazepine receptor complex in dorsal compared to ventral rat hippocampus

Several studies have indicated a functional differentiation across the septotemporal axis of rat hippocampus. Our previous results have shown that the α1β2γ2-GABAA receptor subtype dominates in dorsal hippocampus (DH), while the α2β1γ2-subtype prevails in ventral hippocampus (VH). We therefore studied possible differences in the pharmacological properties and receptor binding parameters of the GABAA receptor subtypes between DH and VH, by examining: (1)(a) the specific binding of [3H]-flunitrazepam (Benzodiazepine sites agonist) by using quantitative autoradiography, (b) the kinetic parameters of [3H]-flunitrazepam specific binding, by using the “wipe off” technique and (2) the competitive displacement of [3H]-flunitrazepam binding by using zolpidem (selective agonist of the α1-subtype) and L-655,708 (selective inverse agonist of the α5-subtype) and the enhancement of [3H]-flunitrazepam binding by using etomidate (selective positive modulator of the β2-subunit), in an autoradiographical saturation kinetic study. Our results showed in VH compared to DH: (A) lower level of [3H]-flunitrazepam binding, apparently due to weaker binding affinity (higher KD value), since no differences in the Bmax value could be detected, (B) higher IC50 values for zolpidem and lower IC50 values for L-655,708 and (C) higher EC50 values for etomidate. In conclusion, the lower binding for zolpidem and etomidate and the higher binding for L-655,708 observed in VH support the evidence that the α1β2γ2-GABAA receptor subtype dominates in DH and the α5-subtype prevails in VH. Further, our results suggest differential pharmacological effects of the benzodiazepines in DH compared to VH, with the sedative effects being more potent in the dorsal hippocampus.