Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity

Gina L Forster, Ronald B. Pringle, Nicholas J. Mouw, Shawn M. Vuong, Michael J. Watt, Andrew R. Burke, Christopher A. Lowry, Cliff H. Summers, Kenneth J. Renner

Research output: Contribution to journalArticle

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Abstract

Interactions between central corticotropin-releasing factor (CRF) and serotonergic systems are believed to be important for mediating fear and anxiety behaviors. Recently we demonstrated that infusions of CRF into the rat dorsal raphe nucleus result in a delayed increase in serotonin release within the medial prefrontal cortex that coincided with a reduction in fear behavior. The current studies were designed to study the CRF receptor mechanisms and pathways involved in this serotonergic response. Infusions of CRF (0.5 μg/0.5 μL) were made into the dorsal raphe nucleus of urethane-anesthetized rats following either inactivation of the median raphe nucleus by muscimol (25 ng/0.25 μL) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal raphe nucleus with antalarmin (25-50 ng/0.5 μL) or antisauvagine-30 (2 μg/0.5 μL), respectively. Medial prefrontal cortex serotonin levels were measured using in-vivo microdialysis and high-performance liquid chromatography with electrochemical detection. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal raphe nucleus was abolished by inactivation of the median raphe nucleus. Furthermore, antagonism of CRF receptor type 2 but not CRF receptor type 1 in the dorsal raphe nucleus abolished CRF-induced increases in medial prefrontal cortex serotonin. Follow-up studies involved electrical stimulation of the central nucleus of the amygdala, a source of CRF afferents to the dorsal raphe nucleus. Activation of the central nucleus increased medial prefrontal cortex serotonin release. This response was blocked by CRF receptor type 2 antagonism in the dorsal raphe. Overall, these results highlight complex CRF modulation of medial prefrontal cortex serotonergic activity at the level of the raphe nuclei.

Original languageEnglish (US)
Pages (from-to)299-310
Number of pages12
JournalEuropean Journal of Neuroscience
Volume28
Issue number2
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

Fingerprint

Serotonin 5-HT2 Receptors
Raphe Nuclei
Corticotropin-Releasing Hormone
Prefrontal Cortex
Serotonin
Fear
Intralaminar Thalamic Nuclei
Corticotropin-Releasing Hormone Receptors
Muscimol
Urethane
Microdialysis
Dorsal Raphe Nucleus
Electric Stimulation
Anxiety
High Pressure Liquid Chromatography

Keywords

  • Central nucleus of the amygdala
  • Microdialysis
  • Muscimol
  • Rat
  • Stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity. / Forster, Gina L; Pringle, Ronald B.; Mouw, Nicholas J.; Vuong, Shawn M.; Watt, Michael J.; Burke, Andrew R.; Lowry, Christopher A.; Summers, Cliff H.; Renner, Kenneth J.

In: European Journal of Neuroscience, Vol. 28, No. 2, 01.07.2008, p. 299-310.

Research output: Contribution to journalArticle

Forster, Gina L ; Pringle, Ronald B. ; Mouw, Nicholas J. ; Vuong, Shawn M. ; Watt, Michael J. ; Burke, Andrew R. ; Lowry, Christopher A. ; Summers, Cliff H. ; Renner, Kenneth J. / Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity. In: European Journal of Neuroscience. 2008 ; Vol. 28, No. 2. pp. 299-310.
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