QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (100) Citing Articles via Google Scholar Google Scholar Articles by Lowry, C. A. Articles by Ingram, C. D. Search for Related Content PubMed PubMed Citation Articles by Lowry, C. A. Articles by Ingram, C. D.

 Previous Article  |  Next Article 

The Journal of Neuroscience, October 15, 2000, 20(20):7728-7736

Corticotropin-Releasing Factor Increases In Vitro Firing Rates of Serotonergic Neurons in the Rat Dorsal Raphe Nucleus: Evidence for Activation of a Topographically Organized Mesolimbocortical Serotonergic System

Christopher A. Lowry, Joanne E. Rodda, Stafford L. Lightman, and Colin D. Ingram

University of Bristol, University Research Centre for Neuroendocrinology, Bristol, BS2 8HW, United Kingdom

In vivo studies suggest that the stress-related neuropeptide corticotropin-releasing factor (CRF) modulates serotonergic neurotransmission. To investigate the underlying mechanisms for this interaction, the present study examined the effects of CRF in vitro on dorsal raphe neurons that displayed electrophysiological and pharmacological properties consistent with a serotonergic phenotype. In the presence of either 1 or 2 mM Ca²⁺, perfusion of ovine CRF or rat/human CRF rapidly and reversibly increased firing rates of a subpopulation (19 of 70, 27%) of serotonergic neurons predominantly located in the ventral portion of the dorsal raphe nucleus. For a given responsive neuron, the excitatory effects of CRF were reproducible, and there was no tachyphylaxis. Excitatory effects were dose-dependent (over the range of 0.1-1.6 µM) and were completely absent after exposure to the competitive CRF receptor antagonists -helical CRF_9-41 or rat/human [D-Phe¹², Nle^21,38, -Me-Leu³⁷]-CRF_12-41. Both the proportion of responsive neurons and the magnitude of excitatory responses to CRF in the ventral portion of the caudal dorsal raphe nucleus were markedly potentiated in slices prepared from animals previously exposed to isolation and daily restraint stress for 5 d. Immunohistochemical staining of the recorded slices revealed close associations between CRF-immunoreactive varicose axons and tryptophan hydroxylase-immunoreactive neurons in the area of the recordings, providing anatomical evidence for potential direct actions of CRF on serotonergic neurons. The electrophysiological properties and the distribution of responsive neurons within the dorsal raphe nucleus are consistent with the hypothesis that endogenous CRF activates a topographically organized mesolimbocortical serotonergic system.

Key words: anxiety; conditioned fear; corticotropin-releasing hormone; CRF; CRH; drug addiction; drug withdrawal; serotonin; mesolimbic; mesolimbocortical; serotonergic; restraint; isolation; sensitization; stress

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20207728-09$05.00/0

This article has been cited by other articles:

				J. G. McEuen, S. G. Beck, and T. L. Bale Failure to Mount Adaptive Responses to Stress Results in Dysregulation and Cell Death in the Midbrain Raphe J. Neurosci., August 13, 2008; 28(33): 8169 - 8177. [Abstract] [Full Text] [PDF]

				J. R. Miragaya and R. B. S. Harris Antagonism of corticotrophin-releasing factor receptors in the fourth ventricle modifies responses to mild but not restraint stress Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R404 - R416. [Abstract] [Full Text] [PDF]

				L. N. Cornelisse, J. E. Van der Harst, J. C. Lodder, P.J.J. Baarendse, A. J. Timmerman, H. D. Mansvelder, B. M. Spruijt, and A. B. Brussaard Reduced 5-HT1A- and GABAB Receptor Function in Dorsal Raphe Neurons Upon Chronic Fluoxetine Treatment of Socially Stressed Rats J Neurophysiol, July 1, 2007; 98(1): 196 - 204. [Abstract] [Full Text] [PDF]

				C. A. Mohila and S.-P. Onn Increases in the Density of Parvalbumin-immunoreactive Neurons in Anterior Cingulate Cortex of Amphetamine-withdrawn Rats: Evidence for Corticotropin-releasing Factor in Sustained Elevation Cereb Cortex, March 1, 2005; 15(3): 262 - 274. [Abstract] [Full Text] [PDF]

				V. B. Risbrough, R. L. Hauger, A. L. Roberts, W. W. Vale, and M. A. Geyer Corticotropin-Releasing Factor Receptors CRF1 and CRF2 Exert Both Additive and Opposing Influences on Defensive Startle Behavior J. Neurosci., July 21, 2004; 24(29): 6545 - 6552. [Abstract] [Full Text] [PDF]

				H. Tan, P. Zhong, and Z. Yan Corticotropin-Releasing Factor and Acute Stress Prolongs Serotonergic Regulation of GABA Transmission in Prefrontal Cortical Pyramidal Neurons J. Neurosci., May 26, 2004; 24(21): 5000 - 5008. [Abstract] [Full Text] [PDF]

				L. Pernar, A. L. Curtis, W. W. Vale, J. E. Rivier, and R. J. Valentino Selective Activation of Corticotropin-Releasing Factor-2 Receptors on Neurochemically Identified Neurons in the Rat Dorsal Raphe Nucleus Reveals Dual Actions J. Neurosci., February 11, 2004; 24(6): 1305 - 1311. [Abstract] [Full Text] [PDF]

				V. Compan, M. Zhou, R. Grailhe, R. A. Gazzara, R. Martin, J. Gingrich, A. Dumuis, D. Brunner, J. Bockaert, and R. Hen Attenuated Response to Stress and Novelty and Hypersensitivity to Seizures in 5-HT4 Receptor Knock-Out Mice J. Neurosci., January 14, 2004; 24(2): 412 - 419. [Abstract] [Full Text] [PDF]

				A. D. Le, S. Harding, W. Juzytsch, P. J. Fletcher, and Y. Shaham The Role of Corticotropin-Releasing Factor in the Median Raphe Nucleus in Relapse to Alcohol J. Neurosci., September 15, 2002; 22(18): 7844 - 7849. [Abstract] [Full Text] [PDF]

				M. A. Pelleymounter, M. Joppa, N. Ling, and A. C. Foster Pharmacological Evidence Supporting a Role for Central Corticotropin-Releasing Factor2 Receptors in Behavioral, but not Endocrine, Response to Environmental Stress J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 145 - 152. [Abstract] [Full Text] [PDF]

				N. Greenberg, J. A. Carr, and C. H. Summers Causes and Consequences of Stress Integr. Comp. Biol., July 1, 2002; 42(3): 508 - 516. [Abstract] [Full Text] [PDF]

				S. E. Hammack, K. J. Richey, M. J. Schmid, M. L. LoPresti, L. R. Watkins, and S. F. Maier The Role of Corticotropin-Releasing Hormone in the Dorsal Raphe Nucleus in Mediating the Behavioral Consequences of Uncontrollable Stress J. Neurosci., February 1, 2002; 22(3): 1020 - 1026. [Abstract] [Full Text] [PDF]

				M. L. Price and I. Lucki Regulation of Serotonin Release in the Lateral Septum and Striatum by Corticotropin-Releasing Factor J. Neurosci., April 15, 2001; 21(8): 2833 - 2841. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help