An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone.
Previous work suggests that the elevated plus-maze test of anxiety is insensitive to the anxiolytic effects of the novel anxiolytic buspirone, which shows an anxiogenic-like profile in this test. This paper examines some of the possible reasons for this and the role that buspirone's agonist activity at 5-HT1A receptors plays in this effect. A variety of 5-HT1A receptor agonists (p-aminophenylethyl-m-trifluromethylphenyl piperazine, (+)- and (-)-MDL 72832) showed similar activity to buspirone, as did the related compound ipsapirone. (-)-MDL 72832 was more potent than (+)-MDL 72832, in keeping with its stereoselective action at 5-HT1A receptors. The alpha 2-adrenoceptor antagonist properties of 1-pyrimidinyl piperazine, a metabolite of buspirone, did not appear to be relevant to this action of buspirone as neither it nor idazoxan showed an anxiogenic-like profile. Neither chronic treatment with buspirone (1 mg/kg SC twice a day for 16 days) nor depletion of 5-HT with p-chlorophenylalanine changed the anxiogenic-like activity of buspirone in the elevated plus-maze test. These results suggest that an agonist action at postsynaptic 5-HT1A receptors mediates the anxiogenic-like effects of buspirone in the elevated plus-maze test and that this test may either be insensitive to certain classes of anxiolytics or is measuring something unrelated to human anxiety states.
Moser
P C
PC
Merrell Dow Research Institute, Strasbourg, France.
D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000031:analogs & derivatives / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects
D011985:Receptors, Serotonin; C037921:1-(2-pyrimidinyl)piperazine; D003975:Diazepam; D010134:Fenclonine; D002065:Buspirone