Serotonergic mechanisms in anxiolytic effect of tandospirone in the Vogel conflict test.
To clarify which 5-HT1A receptors, autoreceptors located in the raphe nuclei or post-synaptic receptors in the forebrain areas receiving a 5-HT input, mediate the anticonflict action of tandospirone (a 5-HT1A receptor-related anxiolytics), the behavioral effects of tandospirone were studied in 5,7-dihydroxytryptamine (5,7-DHT) treated rats. By measuring both monoamines and their metabolite levels and densities of [3H]8-OH-DPAT binding in 5,7-DHT-treated rat brain, we confirmed that pretreatment with 5,7-DHT destroyed 5-HT neurons selectively without affecting postsynaptic 5-HT1A receptors located on the postsynaptic neurons. This selective destruction produced no significant changes in the drinking behavior of rats in either punished or unpunished sessions of the Vogel conflict test. Furthermore, this destruction altered neither the effect of tandospirone on punished responding in this procedure nor the potency of tandospirone to induce a flat body posture in rats, which is known as the "serotonin behavioral syndrome". These results suggested that the anticonflict action of tandospirone may be produced, at least in part, by binding to postsynaptic 5-HT1A receptors and activating them as agonists, and not to 5-HT1A autoreceptors located on the cell bodies of 5-HT neurons.
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
H
H
Shimizu
T
T
Tatsuno
H
H
Tanaka
A
A
Hirose
Y
Y
Araki
M
M
Nakamura
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003220:Conflict, Psychological; D004298:Dopamine / Q000378:metabolism; D054833:Isoindoles; D008297:Male; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C055267:tandospirone; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D004298:Dopamine; D009638:Norepinephrine