Effects of a single or repeated administration of the benzodiazepine inverse agonist FG7142 on behaviour and cortical adrenoceptor binding in the rat.

We have reported previously an increase in the number of beta-adrenoceptors in mouse cerebral cortex 7 days after kindling of seizures by repeated once-daily administration of the benzodiazepine receptor inverse agonist, FG7142. In subsequent experiments, an even larger increase in beta-adrenoceptor number was found 7 days after a single injection of this compound. The present experiments investigated whether FG7142-induced changes in adrenoceptor binding are also found in the rat and whether the effects of a single and repeated injections of this drug differ quantitatively. In view of the anxiogenic effects of FG7142, we have also tested for parallel changes in behaviours associated with anxiety and exploration. Nine days after a single injection of FG7142, the number of beta-adrenoceptors in the cerebral cortex was greater than that found after repeated administration of this compound; this difference was statistically significant. There was no difference in beta-adrenoceptor binding to tissues from chronically FG7142-treated and vehicle-injected animals and there were no changes in alpha 2-adrenoceptor binding or noradrenaline levels after either a single or repeated FG7142 treatment. Neither single nor repeated FG7142 treatment modified spontaneous behaviour in either the elevated plus-maze test of anxiety or the holeboard test of exploration. The behavioural effects of yohimbine and clenbuterol in these tests were also unaffected by FG7142. We discuss the possibility that the difference in the effects of a single and repeated administration of FG7142 on beta-adrenoceptor binding is related to the expression of kindled seizures.