AN AUTORADIOGRAPHICAL SATURATION KINETIC-STUDY OF THE DIFFERENT BENZODIAZEPINE BINDING-SITES IN RAT-BRAIN BY USING [H-3] FLUNITRAZEPAM AS ARADIOLIGAND

The present study reports on the equilibrium association constant (K-D ) and receptor density (B-max) values of a number of brain areas from the mesencephalon, cerebral cortex, hippocampus, and cerebellum for th e overall benzodiazepine (BZ) binding sites as well as for benzodiazep ine binding site subtype 1 (BZ1) and subtype 2 (BZ2), determined by au toradiographical procedures using [H-3] flunitrazepam. The differences between BZ1 and BZ2 binding sites were analyzed using the specific BZ 1 agonist zolpidem as inhibitor of the radioligand. Statistically sign ificant differences in the affinities of BZ2 with respect to BZ and BZ 1 binding sites were mainly found in cortical layers when pK(D) (negat ive logarithms of K, values) values were compared (ANOVA-SNK test). Th e distribution of B-max, as well as the percentages of BZ1 and BZ2 and Hill coefficients which, surprisingly, are always close to 1 (>0.9) f or all the saturation kinetics analyzed, are also described. The possi bility of heterogeneity related to anatomical distribution in the diff erent subtypes is discussed.