1993 Fiscal Year Final Research Report Summary
Neuropharmacological studies on sex difference in the central effects of serotonin1A agonists
| Project/Area Number |
04671413
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
MATSUDA Toshio Osaka Univ. Faculty of Pharmaceutical Sciences, Associate Prof., 薬学部, 助教授 (00107103)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
BABA Akemichi Osaka Univ. Faculty of Pharmaceutical Sciences, Prof., 薬学部, 教授 (70107100)
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Keywords | Serotonin / Sex difference / CRF / Corticosterone / Adenylate cyclase |
|---|
| Research Abstract |
Neuropharmacological studies on the sex differences in the effects of sserotonin _<1A> (5-HT _<1A>) receptor agonists were carried out, in order to clarify the roles of sex hormone in functional relationship between serotonergic system and CRF.
1. CRF stimulated the activity of adenylate cylase in membrane fraction of rat and mouse cerebral cortex and in homogenate of rat pituitary. There is sex difference in the stimulation. Chronic administration of 8-OH-DPAT, a typical 5-HT _<1A> agonist, did not affect CRF-stimulated adenylate cyclase activity in rat pituitary.
2. CRF stimulated tyrosine hydorxylase activity a little in rat brain synaptosomes.
3. Chronic administration of 8-OH-DPAT attenuated the increasing effect of serum corticosterone and the hypothermic effect in mice. The tolerance was observed in female mice faster than in male.
4.Forced swimming stress, which releases CRF, stimulated norepinephrine metabolism, but not 5-HT metabolsim, in hypothalamus of rats.
5.5-HT _<1A> receptor agonists did not affect interacellular Ca ^<2+> level, cAMP level and phosphoinositide metabolism in cultured rat astrocytes,
These findings suggest that the sex difference in the effect of 5-HT _<1A> receptor agonists on hypotalumus-pituitary-adrenal axis is due to that in CRF release. Futher, the sex differences in the postsynaptic effects of 5-HT _<1A> receptor agonists does not appear to be due to those in the receptor and signal transduction systems.
|
