Different location of benzodiazepine sites involved in gut and behavioral effects of benzodiazepine withdrawal in rats

Abstract

This work was performed to determine if the alterations in gastric emptying induced by precipitated withdrawal are linked to peripherally or centrally located benzodiazepine sites, in rats treated chronically with diazepam (15 mg/kg/day IP) for 7 days. In sham-capsaicin-treated rats, precipitated withdrawal by flumazenil (15 mg/kg IP) induced an increase of gastric emptying, whereas it had no effect in systemic capsaicin-treated rats. Both groups of animals developed withdrawal syndrome expressed as motor, autonomic, and behavioral signs. On diazepam-dependent rats, central administration of flumazenil (0.15 mg/kg ICV) induced withdrawal syndrome but had no effect on gastric emptying. These preliminary results suggest that benzodiazepine receptors located in the central nervous system are involved in behavioral withdrawal syndrome, whereas benzodiazepine receptors located at the peripheral level are responsible for digestive withdrawal syndrome involving capsaicin-sensitive neurons.