An anxiolytic-like effect of ondansetron disappears in oxazepam-tolerant rats.
In our experiments a drug from the group of 5-HT3 antagonists--ondansetron (OND)--has been used in rats developing tolerance to oxazepam (OXZ). After 7 days of oxazepam administration (5 mg/kg i.p.) a significant decrease in the anxiolytic behavior was observed in the Crawley test. In the rats already partly tolerant to oxazepam, an undiminished anxiolytic-like effect of ondansetron (single injection of 0.1 mg/kg i.p., seventh day) was observed. After 14 days of oxazepam administration its anxiolytic activity was even more diminished. A single injection of ondansetron 0.1 mg/kg restored the anxiolytic behavior: rise of BWT (black-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 influenced in the first stages of tolerance development to oxazepam, but the drug was not able to produce an anxiolytic effect in the state of full tolerance to oxazepam (after 3 weeks).
Nowakowska
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Department of Pharmacology, Medical Academy, Poznań, Poland.
Chodera
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A
Kus
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K
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D004361:Drug Tolerance; D008297:Male; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology*; D010076:Oxazepam / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D017294:Ondansetron; D010076:Oxazepam