Potential anxiolytic properties of R-(+)-8-OSO2CF3-PAT, a 5-HT 1A receptor agonist.
The anxiolytic property of R-(+)-8-OSO2CF3-PAT(R-(+)-8- [[(trifluoromethyl)sulfonyl]oxy]-2-(n-propyl-amino)tetralin), a 5-HT1A receptor agonist, was evaluated in Wistar rats by means of animal models of anxiety, the conditioned defensive burying model and the conditioned stress-induced freezing response followed by the elevated plus-maze test, respectively. In addition, the 5-HIAA/5-HT ratio (5-hydroxy-indole acetic acid/5-hydroxytryptamine) of rat brain homogenates was studied. Acute drug administration resulted in abolition of the burying behaviour (3 mg/kg i.p.), a dose-dependent decrease of rearing and induction of hyperphagia. R-(+)-8-OSO2CF3-PAT had no effect on conditioned footshock-induced freezing behaviour but increased open-arm activity in the rats on the plus-maze. The 5-HIAA/5-HT ratio was decreased in the lateral septum (1 and 3 mg/kg), dorsal hippocampus (3 mg/kg) and somatosensory cortex (3 mg/kg), implying that R-(+)-8-OSO2CF3-PAT affects particularly the limbic system in anxiety-inducing situations.
Barf
T
T
Department of Medicinal Chemistry, University Centre for Pharmacy, Groningen, Netherlands.
Korte
S M
SM
Korte-Bouws
G
G
Sonesson
C
C
Damsma
G
G
Bohus
B
B
Wikström
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D017366:Serotonin Receptor Agonists; C099940:8-(((trifluoromethyl)sulfonyl)oxy)-2-(n-propylamino)tetralin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin