Pentobarbital differentially enhances the affinity of [3H]flunitrazepam binding across brain regions

The present study used saturation binding analyses to test the hypothesis that pentobarbital would differentially increase the affinity of benzodiazepine binding across brain regions. The results showed that there were significant (p < 0.05) regional differences in the dissociation constant (KD) for tritiated flunitrazepam ([3H]FLU) and that pentobarbital differentially decreased the KD for [3H]FLU across 6 brain regions. Pentobarbital caused the greatest decrease (-43%) in KD in the medulla. The results support the concept that type A gamma-aminobutyric acid (GABAA) receptor subtypes are localized differentially throughout the brain. Defining the regional specificity of interactions between benzodiazepines and barbiturates at the GABAA receptor will be important for understanding the mechanisms by which these drugs produce their behavioral effects in vivo.