The anxiolytic-like effects of 5-hydroxytryptamine3 (5-HT3) receptor antagonists.
The effect of six 5-HT3 receptor antagonists: ondansetron (0.01-3 mg/kg ip), granisetron (0.01-1 mg/kg ip), zacopride (0.01-3 mg/kg ip), tropisetron (0.001-0.1 mg/kg ip), MDL 72222 (0.01-3 mg/kg ip) and DAU 6215 (0.01-3 mg/kg sc) were examined in the conflict drinking test (Vogel test) and in the elevated plus-maze test in rats. Ondansetron (0.1-0.3 or 1 mg/kg), zacopride (0.1-1 mg/kg) and tropisetron (0.01 mg/kg) increased the punished responding in the Vogel test and showed anxiolytic effects in the elevated plus-maze test. Their effects were limited to a narrow dose range and were not dose-dependent. Granisetron (0.1 mg/kg) exhibited an anti-conflict activity, but was ineffective in the elevated plus-maze test. MDL 72222 and DAU 6215 were ineffective in both those tests. On the other hand, diazepam (2.5-10 mg/kg), used as a reference drug, was active in either procedure and its effects were dose-dependent. These results indicate that an anxiolytic-like activity is not a common characteristic of 5-HT3 receptor antagonists. Moreover, even the anxiolytic action of drugs which were active in the experimental models used should be accepted with caution.
Filip
M
M
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Baran
L
L
Siwanowicz
J
J
Chojnacka-Wójcik
E
E
Przegaliński
E
E
D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D011678:Punishment; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*
D012702:Serotonin Antagonists