Behavioral profile of the 5HT1A receptor antagonist (S)-UH-301 in rodents and monkeys.
The effects of the new 5HT1A receptor antagonist (S)-UH-301 were investigated in several neurological and behavioral tests in rodents and monkeys. By itself, (S)-UH-301 was found to decrease palatable food consumption in rats, to exhibit anticonvulsant activity in mice, and anxiolytic-like properties in two rodent models of anxiety (light-dark test and elevated plus-maze test). (S)-UH-301 antagonized various symptoms and behaviors induced by the selective 5HT1A receptor agonist 8-OH-DPAT, such as lower lip retraction and flat body posture in rats, hyperphagia for palatable food in rats, and displacement activities (considered as indices of anxiety) in squirrel monkeys. These results further characterize (S)-UH-301 as an in vivo active 5HT1A receptor antagonist and suggest that this antagonistic activity might confer the compound with anxiolytic-like properties.
Moreau
J L
JL
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Griebel
G
G
Jenck
F
F
Martin
J R
JR
Widmer
U
U
Haefely
W E
WE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000161:Acoustic Stimulation; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D004873:Ergolines / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D007650:Ketanserin / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists
D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C064282:UH 301; D012701:Serotonin; D016202:N-Methylaspartate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C031649:mesulergine