Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint

Na Feng, Christopher A. Lowry, Jodi L. Lukkes, Miles Orchinik, Gina L. Forster, Kenneth J. Renner

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The dorsomedial hypothalamus (DMH) has been implicated in the coordination of stress responses. Restraint stress or systemic corticosterone (CORT) treatment induces a rapid increase in tissue concentrations of serotonin (5-hydroxytryptamine; 5-HT) in the DMH. Although the mechanism for rapid changes in 5-HT concentrations in the DMH is not clear, earlier results suggest that stress-induced increases in CORT may inhibit 5-HT transport from the extracellular fluid by acting on corticosterone-sensitive organic cation transporters (OCTs). We tested the hypothesis that perfusion of the medial hypothalamus (MH), which includes the DMH, with the OCT blocker decynium 22 (D-22) would potentiate the effects of mild restraint on extracellular 5-HT. Male Sprague-Dawley rats, implanted with a microdialysis probe into the MH, were treated with reverse-dialysis of D-22 (20 μM; 40 min) or vehicle and subjected to either 40 min mild restraint or undisturbed control conditions. Perfusates collected from a separate group of rats were evaluated for the effect of restraint on extracellular CORT concentrations in the MH. Reverse-dialysis of D-22 induced an increase (200%) in extracellular 5-HT concentrations in the MH in undisturbed control rats. Restraint in the absence of D-22 did not significantly affect MH CORT or 5-HT concentrations. However, perfusion of the MH with D-22 during restraint led to an increased magnitude and duration of extracellular 5-HT concentrations, relative to D-22 by itself. These results are consistent with the hypothesis that OCTs in the DMH contribute to the clearance of 5-HT from the extracellular fluid under both baseline conditions and mild restraint.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalBrain Research
Volume1326
DOIs
StatePublished - Apr 22 2010

Fingerprint

Cations
Serotonin
Middle Hypothalamus
Corticosterone
Hypothalamus
Extracellular Fluid
Dialysis
Perfusion
Microdialysis
Sprague Dawley Rats

Keywords

  • 5-hydroxytryptamine
  • Dorsomedial hypothalamus (DMH)
  • OCT3
  • Organic cation transporter
  • Restraint stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint. / Feng, Na; Lowry, Christopher A.; Lukkes, Jodi L.; Orchinik, Miles; Forster, Gina L.; Renner, Kenneth J.

In: Brain Research, Vol. 1326, 22.04.2010, p. 105-113.

Research output: Contribution to journalArticle

Feng, Na ; Lowry, Christopher A. ; Lukkes, Jodi L. ; Orchinik, Miles ; Forster, Gina L. ; Renner, Kenneth J. / Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint. In: Brain Research. 2010 ; Vol. 1326. pp. 105-113.
@article{306d953f99684b2fb79351d9315785d3,
title = "Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint",
abstract = "The dorsomedial hypothalamus (DMH) has been implicated in the coordination of stress responses. Restraint stress or systemic corticosterone (CORT) treatment induces a rapid increase in tissue concentrations of serotonin (5-hydroxytryptamine; 5-HT) in the DMH. Although the mechanism for rapid changes in 5-HT concentrations in the DMH is not clear, earlier results suggest that stress-induced increases in CORT may inhibit 5-HT transport from the extracellular fluid by acting on corticosterone-sensitive organic cation transporters (OCTs). We tested the hypothesis that perfusion of the medial hypothalamus (MH), which includes the DMH, with the OCT blocker decynium 22 (D-22) would potentiate the effects of mild restraint on extracellular 5-HT. Male Sprague-Dawley rats, implanted with a microdialysis probe into the MH, were treated with reverse-dialysis of D-22 (20 μM; 40 min) or vehicle and subjected to either 40 min mild restraint or undisturbed control conditions. Perfusates collected from a separate group of rats were evaluated for the effect of restraint on extracellular CORT concentrations in the MH. Reverse-dialysis of D-22 induced an increase (200{\%}) in extracellular 5-HT concentrations in the MH in undisturbed control rats. Restraint in the absence of D-22 did not significantly affect MH CORT or 5-HT concentrations. However, perfusion of the MH with D-22 during restraint led to an increased magnitude and duration of extracellular 5-HT concentrations, relative to D-22 by itself. These results are consistent with the hypothesis that OCTs in the DMH contribute to the clearance of 5-HT from the extracellular fluid under both baseline conditions and mild restraint.",
keywords = "5-hydroxytryptamine, Dorsomedial hypothalamus (DMH), OCT3, Organic cation transporter, Restraint stress",
author = "Na Feng and Lowry, {Christopher A.} and Lukkes, {Jodi L.} and Miles Orchinik and Forster, {Gina L.} and Renner, {Kenneth J.}",
year = "2010",
month = "4",
day = "22",
doi = "10.1016/j.brainres.2010.02.044",
language = "English (US)",
volume = "1326",
pages = "105--113",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint

AU - Feng, Na

AU - Lowry, Christopher A.

AU - Lukkes, Jodi L.

AU - Orchinik, Miles

AU - Forster, Gina L.

AU - Renner, Kenneth J.

PY - 2010/4/22

Y1 - 2010/4/22

N2 - The dorsomedial hypothalamus (DMH) has been implicated in the coordination of stress responses. Restraint stress or systemic corticosterone (CORT) treatment induces a rapid increase in tissue concentrations of serotonin (5-hydroxytryptamine; 5-HT) in the DMH. Although the mechanism for rapid changes in 5-HT concentrations in the DMH is not clear, earlier results suggest that stress-induced increases in CORT may inhibit 5-HT transport from the extracellular fluid by acting on corticosterone-sensitive organic cation transporters (OCTs). We tested the hypothesis that perfusion of the medial hypothalamus (MH), which includes the DMH, with the OCT blocker decynium 22 (D-22) would potentiate the effects of mild restraint on extracellular 5-HT. Male Sprague-Dawley rats, implanted with a microdialysis probe into the MH, were treated with reverse-dialysis of D-22 (20 μM; 40 min) or vehicle and subjected to either 40 min mild restraint or undisturbed control conditions. Perfusates collected from a separate group of rats were evaluated for the effect of restraint on extracellular CORT concentrations in the MH. Reverse-dialysis of D-22 induced an increase (200%) in extracellular 5-HT concentrations in the MH in undisturbed control rats. Restraint in the absence of D-22 did not significantly affect MH CORT or 5-HT concentrations. However, perfusion of the MH with D-22 during restraint led to an increased magnitude and duration of extracellular 5-HT concentrations, relative to D-22 by itself. These results are consistent with the hypothesis that OCTs in the DMH contribute to the clearance of 5-HT from the extracellular fluid under both baseline conditions and mild restraint.

AB - The dorsomedial hypothalamus (DMH) has been implicated in the coordination of stress responses. Restraint stress or systemic corticosterone (CORT) treatment induces a rapid increase in tissue concentrations of serotonin (5-hydroxytryptamine; 5-HT) in the DMH. Although the mechanism for rapid changes in 5-HT concentrations in the DMH is not clear, earlier results suggest that stress-induced increases in CORT may inhibit 5-HT transport from the extracellular fluid by acting on corticosterone-sensitive organic cation transporters (OCTs). We tested the hypothesis that perfusion of the medial hypothalamus (MH), which includes the DMH, with the OCT blocker decynium 22 (D-22) would potentiate the effects of mild restraint on extracellular 5-HT. Male Sprague-Dawley rats, implanted with a microdialysis probe into the MH, were treated with reverse-dialysis of D-22 (20 μM; 40 min) or vehicle and subjected to either 40 min mild restraint or undisturbed control conditions. Perfusates collected from a separate group of rats were evaluated for the effect of restraint on extracellular CORT concentrations in the MH. Reverse-dialysis of D-22 induced an increase (200%) in extracellular 5-HT concentrations in the MH in undisturbed control rats. Restraint in the absence of D-22 did not significantly affect MH CORT or 5-HT concentrations. However, perfusion of the MH with D-22 during restraint led to an increased magnitude and duration of extracellular 5-HT concentrations, relative to D-22 by itself. These results are consistent with the hypothesis that OCTs in the DMH contribute to the clearance of 5-HT from the extracellular fluid under both baseline conditions and mild restraint.

KW - 5-hydroxytryptamine

KW - Dorsomedial hypothalamus (DMH)

KW - OCT3

KW - Organic cation transporter

KW - Restraint stress

UR - http://www.scopus.com/inward/record.url?scp=77950033374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950033374&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2010.02.044

DO - 10.1016/j.brainres.2010.02.044

M3 - Article

C2 - 20171957

AN - SCOPUS:77950033374

VL - 1326

SP - 105

EP - 113

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -