A single dose of FG 7142 causes long-term increases in mouse cortical beta-adrenoceptors.

There is evidence that central monoamines are involved in the actions of benzodiazepines. We have investigated the effects of a single dose of the benzodiazepine partial inverse agonist, FG 7142, on radioligand binding to alpha 2- and beta-adrenoceptors in mouse cerebral cortex. We found that seven days after a single injection of FG 7142 there was a large increase in the density of beta-adrenoceptors. This rise was not detectable either 15-30 min, or 24 h after the injection and no statistically significant changes in alpha 2-adrenoceptor binding were found at any of these times. Administration of the benzodiazepine antagonist Ro 15-1788 at the same time as FG 7142 prevented the rise in beta-adrenoceptor density. We discuss the possibility that the beta-adrenoceptor upregulation is related to the behavioural effects of FG 7142.