AN ANXIOLYTIC-LIKE EFFECT OF ONDANSETRON DISAPPEARS IN OXAZEPAM-TOLERANT RATS

In our experiments a drug from the group of 5-HT3 antagonists-ondanset ron (OND)-has been used in rats developing tolerance to oxazepam (OXZ) . After 7 days of oxazepam administration (5 mg/kg IP) a significant d ecrease in the anxiolytic behavior was observed in the Crawley test. I n the rats already partly tolerant to oxazepam, an undiminished anxiol ytic-like effect of ondansetron (single injection of 0.1 mg/kg IF, sev enth day) was observed. After 14 days of oxazepam administration its a nxiolytic activity was even more diminished. A single injection of ond ansetron 0.1 mg/kg restored the anxiolytic behavior: rise of BWT (blac k-white transition) and WSE (white square entrance). After 21 days the anxiolytic activity of oxazepam was totally abolished and the single injection of ondansetron did not restore the state of anxiolysis. The results show that the anxiolytic effects of ondansetron were not influ enced in the first stages of tolerance development to oxazepam, but th e drug was not able to produce an anxiolytic effect in the state of fu ll tolerance to oxazepam (after 3 weeks). (C) 1998 Elsevier Science In c.