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.
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