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The role of corticosterone-sensitive...

University of South Dakota.

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The role of corticosterone-sensitive organic cation transporters in stress-mediated serotonergic signaling in the rat medial hypothalamus.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The role of corticosterone-sensitive organic cation transporters in stress-mediated serotonergic signaling in the rat medial hypothalamus./
Author:	Feng, Na.
Description:	198 p.
Notes:	Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1502.
Contained By:	Dissertation Abstracts International70-03B.
Subject:	Biology, Neuroscience. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3351177
ISBN:	9781109069891

The role of corticosterone-sensitive organic cation transporters in stress-mediated serotonergic signaling in the rat medial hypothalamus.
Feng, Na.

The role of corticosterone-sensitive organic cation transporters in stress-mediated serotonergic signaling in the rat medial hypothalamus. - 198 p.

Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1502.

Thesis (Ph.D.)--University of South Dakota, 2008.

The dorsomedial hypothalamus (DMH) coordinates physiological and behavioral responses to stress. Acute corticosterone (CORT) treatment or exposure to stress rapidly increase tissue levels of 5-HT in the DMH. The mechanism for this effect is unknown. The experiments in this dissertation tested the hypothesis that CORT inhibits the clearance of extracellular 5-HT released in response to stress through inhibition of CORT-sensitive organic cation transporters (OCTs). OCTs are low-affinity, high-capacity transporters that have been recently identified in the DMH. The first study was designed to determine if the OCT blocker, decynium 22 (D-22), delivered by reverse microdialysis into the medial hypothalamus (MH), including the DMH, increased extracellular 5-HT and induced anxiogenic behaviors in male rats. Intra-MH D-22 dose-dependently and reversibly increased MH 5-HT levels and the highest dose of D-22 (100 muM) induced increases in grooming behavior suggesting that OCTs in the MH are functional. The effect of intra-MH CORT on extracellular 5-HT was then tested under conditions in which 5-HT activity was pharmacologically augmented by the 5-HT releasing agent, D-fenfluramine, or physiologically, by acute restraint stress. In rats treated with either intraperitoneal or intra-MH D-fenfluramine (1 mg/kg or 5 muM, respectively) and intra-MH CORT (200 ng/mL aCSF), CORT potentiated the magnitude and duration of D-fenfluramine-induced increases in extracellular 5-HT relative to vehicle-treated controls. Consistent with this finding, acute restraint stress, which enhances 5-HT activity and induces CORT release, potentiated the effect of submaximal OCT inhibition by 20 muM D-22 on MH extracellular 5-HT relative to unrestrained D-22-treated controls. These results suggest that the effect of CORT on OCT-mediated 5-HT transport in the MH is significant under conditions where serotonergic activity is increased. In the fourth study, the effects of intra-MH CORT on 5-HT were tested in the presence or absence of ovarian steroids in ovariectomized rats. Simultaneous delivery of infra-MH CORT (200 ng/mL aCSF) and progesterone (120 ng/mL aCSF) increased extracellular 5-HT in females primed with systemic 17 beta-estradiol (5 mug). Taken together, the results support the hypothesis that CORT inhibits OCTs-regulated 5-HT transport in the DMH and may serve to augment serotonergic neurotransmission in response to stressful stimuli.

ISBN: 9781109069891Subjects--Topical Terms:

1017680
Biology, Neuroscience.

The role of corticosterone-sensitive organic cation transporters in stress-mediated serotonergic signaling in the rat medial hypothalamus.
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100 1 $a Feng, Na. $3 1021849
245 1 4 $a The role of corticosterone-sensitive organic cation transporters in stress-mediated serotonergic signaling in the rat medial hypothalamus.
300 $a 198 p.
500 $a Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1502.
502 $a Thesis (Ph.D.)--University of South Dakota, 2008.
520 $a The dorsomedial hypothalamus (DMH) coordinates physiological and behavioral responses to stress. Acute corticosterone (CORT) treatment or exposure to stress rapidly increase tissue levels of 5-HT in the DMH. The mechanism for this effect is unknown. The experiments in this dissertation tested the hypothesis that CORT inhibits the clearance of extracellular 5-HT released in response to stress through inhibition of CORT-sensitive organic cation transporters (OCTs). OCTs are low-affinity, high-capacity transporters that have been recently identified in the DMH. The first study was designed to determine if the OCT blocker, decynium 22 (D-22), delivered by reverse microdialysis into the medial hypothalamus (MH), including the DMH, increased extracellular 5-HT and induced anxiogenic behaviors in male rats. Intra-MH D-22 dose-dependently and reversibly increased MH 5-HT levels and the highest dose of D-22 (100 muM) induced increases in grooming behavior suggesting that OCTs in the MH are functional. The effect of intra-MH CORT on extracellular 5-HT was then tested under conditions in which 5-HT activity was pharmacologically augmented by the 5-HT releasing agent, D-fenfluramine, or physiologically, by acute restraint stress. In rats treated with either intraperitoneal or intra-MH D-fenfluramine (1 mg/kg or 5 muM, respectively) and intra-MH CORT (200 ng/mL aCSF), CORT potentiated the magnitude and duration of D-fenfluramine-induced increases in extracellular 5-HT relative to vehicle-treated controls. Consistent with this finding, acute restraint stress, which enhances 5-HT activity and induces CORT release, potentiated the effect of submaximal OCT inhibition by 20 muM D-22 on MH extracellular 5-HT relative to unrestrained D-22-treated controls. These results suggest that the effect of CORT on OCT-mediated 5-HT transport in the MH is significant under conditions where serotonergic activity is increased. In the fourth study, the effects of intra-MH CORT on 5-HT were tested in the presence or absence of ovarian steroids in ovariectomized rats. Simultaneous delivery of infra-MH CORT (200 ng/mL aCSF) and progesterone (120 ng/mL aCSF) increased extracellular 5-HT in females primed with systemic 17 beta-estradiol (5 mug). Taken together, the results support the hypothesis that CORT inhibits OCTs-regulated 5-HT transport in the DMH and may serve to augment serotonergic neurotransmission in response to stressful stimuli.
590 $a School code: 0203.
650 4 $a Biology, Neuroscience. $3 1017680
690 $a 0317
710 2 $a University of South Dakota. $3 1019292
773 0 $t Dissertation Abstracts International $g 70-03B.
790 $a 0203
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3351177