Effect of chronic ipsapirone treatment on the density of 5-HT1A receptors and 5-HT1A receptor mRNA in discrete regions of the rat brain.
There is increasing evidence that the 5-hydroxytryptamine (HT)1A partial agonist ipsapirone is an effective anxiolytic/antidepressant agent, although its mechanism of action is not clear. In this study, we investigated the effects of chronic ipsapirone treatment (5 or 10 mg/kg; twice daily, 3 weeks) on 5-HT1A receptor density 8-hydroxy-2-(di-n-propyl amino) tetralin (8O H-DPAT) binding and the level of its mRNA (in situ hybridization) in various regions of the rat (male Wistar 250 g) brain. Receptor density was reduced in the frontal cortex, but did not change significantly in the hippocampus and dorsal raphe nucleus. The level of receptor mRNA was unchanged in each of these brain regions. The present results suggest that the clinical anxiolytic effects of ipsapirone may be mediated partly by postsynaptic action on serotonergic transmission in the frontal cortex, but not in the hippocampus or dorsal raphe nuclei.
Shiro
Y
Y
Department of Neurology, Okayama University Medical School, Japan.
Fujiwara
Y
Y
Hikiji
M
M
Hamamura
T
T
Shomori
T
T
Kuroda
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D011743:Pyrimidines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C043077:ipsapirone