DIFFERENTIAL-EFFECTS ON GABA(A) RECEPTOR GAMMA(2)-SUBUNIT MESSENGER-RNA BY TOLERANCE TO AND WITHDRAWAL FROM PENTOBARBITAL - AN IN-SITU HYBRIDIZATION STUDY

The heterogeneity of the GABA(A) receptors has been confirmed structur ally and functionally. The present study demonstrates the pharmacologi cal heterogeneity of the GABA(A) receptors. Rats were rendered toleran t to pentobarbital by continuous intracerebroventricular infusion via osmotic minipumps and abruptly withdrawn from pentobarbital. In situ h ybridization of mRNA coding for the GABA(A) receptor gamma2-subunit sh owed decreases of mRNA levels in superior and inferior colliculus in p entobarbital tolerant rats compared to rats in withdrawal. In rats 24- hr after withdrawal from pentobarbital, increases of mRNA levels in ne ocortex, piriform cortex and in granular and Purkinje cell layers of t he cerebellum were observed. These results indicate the fast adaptatio n of GABA synapses in response to abrupt withdrawal from chronic pento barbital treatment. The differential responsiveness seen in different areas further confirms the pharmacological heterogeneity of the GABA(A ) receptors. The observed increases and decreases of mRNA may underlie , at least in part, the previously reported changes in Bmax of GABA(A) receptor ligand binding sites.