Local perfusion of corticosterone in the rat medial hypothalamus potentiates d-fenfluramine-induced elevations of extracellular 5-HT concentrations

Na Feng, Martin Telefont, Kyle J. Kelly, Miles Orchinik, Gina L. Forster, Kenneth J. Renner, Christopher A. Lowry

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The dorsomedial hypothalamus (DMH) plays an important role in coordinating physiological and behavioral responses to stress-related stimuli. In vertebrates, DMH serotonin (5-HT) concentrations increase rapidly in response to acute stressors or corticosterone (CORT). Recent studies suggest that CORT inhibits postsynaptic clearance of 5-HT from the extracellular fluid in the DMH by blocking organic cation transporter 3 (OCT3), a polyspecific CORT-sensitive transport protein. Because OCTs are low-affinity, high-capacity transporters, we hypothesized that CORT effects on extracellular 5-HT are most pronounced in the presence of elevated 5-HT release. We predicted that local application of CORT into the DMH would potentiate the effects of d-fenfluramine, a 5-HT-releasing agent, on extracellular 5-HT. These experiments were conducted using in vivo microdialysis in freely-moving male Sprague-Dawley rats implanted with a microdialysis probe into the medial hypothalamus (MH), which includes the DMH. In Experiment 1, rats simultaneously received intraperitoneal (i.p.) injections of 1 mg/kg d-fenfluramine or saline and either 200 ng/mL CORT or dilute ethanol (EtOH) vehicle delivered to the MH by reverse-dialysis for 40 min. In Experiment 2, 5 μM d-fenfluramine and either 200 ng/mL CORT or EtOH vehicle were concurrently delivered to the MH for 40 min using reverse-dialysis. CORT potentiated the increases in extracellular 5-HT concentrations induced by either i.p. or intra-MH administration of d-fenfluramine. Furthermore, CORT and d-fenfluramine interacted to alter home cage behaviors. Our results support the hypothesis that CORT inhibition of OCT3-mediated 5-HT clearance from the extracellular fluid contributes to stress-induced increases in extracellular 5-HT and 5-HT signaling.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalHormones and Behavior
Issue number1
StatePublished - Jun 2009
Externally publishedYes


  • 5-hydroxytryptamine
  • Corticosterone
  • Dorsomedial hypothalamus
  • EMT
  • Extraneuronal monoamine transporter
  • OCT3
  • Organic cation transporter
  • Serotonin
  • Stress
  • Uptake 2

ASJC Scopus subject areas

  • Endocrinology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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