DIFFERENTIAL PROPERTIES OF TYPE-I AND TYPE-II BENZODIAZEPINE RECEPTORS IN MAMMALIAN CNS NEURONS

1 The effects of benzodiazepine receptor (BZR) partial agonists, Y-236 84 and CL218,872, were compared with its full agonist, diazepam, on ga mma-aminobutyric acid (GABA)-induced Cl- current (I(Cl)) in acutely di ssociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spi nal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp te chnique. 2 The GABA-induced responses were essentially the same in bot h SVH and CPJ neurones, but the K(D) value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3 Enhanc ement of the GABA response by the two partial agonists was about one-t hird of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ2, is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ1, is predominant). In CTX neurones where both ty pe I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4 In concentration-response relationships of BZR partial agonists, the threshold concentrations, K(D) values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Al so, in all preparations, the threshold concentration and K(D) values o f diazepam action were 10 fold less than those induced by partial agon ists. 5 All BZR agonists shifted the concentration-response relationsh ip for GABA to the left without changing the maximum current amplitude , indicating that activation of both BZ1 and BZ2 increase the affinity of the GABA(A) receptor for GABA. 6 The results are important in clar ifying the mechanism of anxiety and might explain the anxioselectivity of BZR partial agonists.