An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone
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- Moser, P.C. Psychopharmacology (1989) 99: 48. doi:10.1007/BF00634451
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Previous work suggests that the elevated plusmaze 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-aminophenylethylm-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 α2-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 withp-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.