Iontophoretic mapping of corticotropin-releasing factor (CRF) sensitive neurons in the rat forebrain

Eberly, Lewis B.; Dudley, Carol A.; Moss, Robert L.

doi:10.1016/0196-9781(83)90077-3

Cited by 83 publications

(32 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inhibitory effects of CRF in the brain are not unique to the DRN as they have been demonstrated in neurons of the thalamus, lateral septum (Eberly et al 1983), the paraventricular nucleus of the hypothalamus (Siggins et al 1985), and the central nucleus of the amygdala (Rainnie et al 1992). Although the majority of DRN neurons were inhibited by CRF, there was substantial variability in the magnitude and time course of the responses and this was most apparent with i.c.v.…”

Section: Discussionmentioning

confidence: 99%

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

Kirby

Rice

Valentino

2000

Neuropsychopharmacology

278

284

View full text Add to dashboard Cite

The present study examined the regional localization of corticotropin-releasing factor (CRF)-and 5-hydroxytryptamine (5-HT)-immunoreactive (IR) fibers within the rat dorsal raphe nucleus (DRN) using immunohistochemistry. Additionally, the effects of CRF, administered intracerebroventricularly (0.1-3.0 g) or intraraphe (0.3-30 ng), on discharge rates of putative 5-HT DRN neurons Corticotropin-releasing factor (CRF) has a diverse range of physiological and behavioral effects, acting both as a neurohormone at the level of the anterior pituitary and as a neurotransmitter in brain. As a neurohormone, CRF initiates the release of adrenocorticotropic hormone which triggers the endocrine limb of the stress response . Anatomical evidence of a widespread distribution of CRF-immunoreactive (IR) terminals and receptors throughout the brain De Souza et al. 1985;Potter et al. 1994;Sakanaka et al. 1987;Swanson et al. 1983) provides support for the additional role of CRF as a brain neurotransmitter. An example of a potential neurotransmitter action of CRF is its action on the locus coeruleus (LC)-norepinephrine system. Intracerebroventricular (i.c.v.) or intracoerulear administration of CRF increases activity of LC neurons Page and Abercrombie 1999;Valentino et al. 1983) and stimulates NE release in terminal fields of the LC (Lavicky and Dunn 1993;Page and Abercrombie 1999;Smagin et al. 1995). Moreover, activation of LC neurons by certain physiological stimuli is attenuated by CRF antagonists administered into the LC (Curtis et al. 1994;Lechner et al. 1997).Anatomical evidence suggests that CRF is also positioned to affect activity of the dorsal raphe nucleus Philadelphia, PA 19102. Received May 17, 1999; revised July 28, 1999; accepted August 3, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 2 CRF Effects on 5-HT Neurons 149 (DRN)-5-hydroxytryptamine (5-HT) system. Thus, CRF receptor binding sites (De Souza et al. 1985) and mRNA Potter et al. 1994) as well as CRF-IR terminals (Sakanaka et al. 1987;Swanson et al. 1983) are localized in the DRN, a primary site of 5-HT cell bodies projecting to the forebrain. Recent studies demonstrated that relatively low doses of CRF (administered i.c.v.) inhibit 5-HT release in two different terminal regions of the DRN (i.e., striatum and lateral septum), suggesting that the site of action of CRF effects on 5-HT release is at the level of the cell bodies in the DRN . Consistent with this, electrophysiological recordings indicated that a low dose of CRF (administered i.c.v.) that decreased extracellular levels of 5-HT in striatum also decreased DRN discharge rate . In contrast to the effects of low doses of CRF, higher doses were found to not alter or to increase extracellular 5-HT levels in the lateral septum or striatum, respectively. The complex dose-related effects of CRF on 5-HT release could be a function of multiple CRF receptor subtypes within the DRN and/or different sites of action (cell bodies vs. terminals) of i.c.v. administered CRF.The present study was designed t...

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

Kirby

Rice

Valentino

2000

Neuropsychopharmacology

278

284

View full text Add to dashboard Cite

show abstract

“…The results of these studies have led to the suggestion that CRF may act as a neurotransmitter or neuromodulator in the CNS, where it appears to play a role in the integration of the organism's responses to stress. A neurotransmitter role for CRF in the rat CNS is further supported by several findings at the cellular level, including its release from brain slices in a calcium-dependent manner following potassium stimulation (Smith et al, 1986), the ability of CRF to alter neuronal firing rates following iontophoretic application (Aldenhoff et al, 1983;Eberly et al, 1983;Valentino et al, 1983), and its ability to promote the formation of CAMP (Wynn et al, 1984;Chen and Bilezikjian, 1985). Recently, we and others have reported the autoradiographic identification and characterization of specific binding sites for iodine-125labeled analogs of ovine CRF in rat (De Souza et al, 1984b, 1985aWynn et al, 1984;De Souza and Kuhar, 1986a, b), monkey (De Souza and Kuhar, 1986a, b) and human (De Souza and Kuhar, 1986b) brain; however, specific binding sites for endogenous CRF remain to be identified and characterized in rat brain.…”

mentioning

confidence: 84%

“…1982;Veldhuis and De Wied, 1984), and decreases in feeding (Morley and Levine, 1982) and sexual (Sirinathsinghji et al, 1983) behaviors. In addition, numerous areas of the brain, including the cortex, hypothalamus, thalamus, and lateral septal area have been shown to be electrophysiologically responsive to iontophoretic application of CRF (Eberly et al, 1983), as Relative values represent the mean + SEM determined from results of 3-5 experiments comparing the levels of IZ51-Tyr" rat/human CRF binding in the absence (total) and presence (blank) of 1 PM rat CRF across all regions and 3-5 experiments in which regional competition curves using increasing concentrations of unlabeled rat CRF were analyzed by EBDA to obtain B,, values.…”

Section: Discussionmentioning

confidence: 99%

Corticotropin-releasing factor receptors in the rat central nervous system: characterization and regional distribution

Souza¹

1987

J. Neurosci.

324

119

View full text Add to dashboard Cite

A stable, iodine-125-labeled analog of rat/human corticotropin- releasing factor (CRF) was used to define the characteristics of CRF receptors in a crude mitochondrial/synaptosomal membrane preparation of rat olfactory bulb, and to study the distribution of CRF binding sites in discrete regions of the rat CNS. The binding of 125I-Tyro rat/human CRF (125I-rCRF) was time- and temperature-dependent, was sensitive to the pH, ionic strength, and cationic composition of the incubation buffer, and was linear over a broad range of membrane protein concentrations. 125I-rCRF binding to olfactory bulb membrane was saturable, reversible, and, on Scatchard analysis, revealed a high- affinity component with an apparent equilibrium dissociation constant (Kd) of 0.2 nM and a low-affinity binding site with Kd of approximately 20 nM. Data from pharmacological studies indicated that the ability of a variety of CRF fragments and analogs to inhibit 125I-rCRF to olfactory bulb membranes correlates well with their reported relative potencies in stimulating pituitary adrenocorticotropic hormone secretion in vitro. Consistent with a coupling of CRF receptors to adenylate cyclase, the binding of 125I-rCRF was decreased by guanine nucleotides and increased by magnesium ions. A heterogeneous distribution of 125I-rCRF binding sites was found in the rat CNS, with highest densities present in olfactory bulb, cerebellum, cerebral cortex and striatum, and progressively lower but significant levels of binding were detected in cervical spinal cord, hypothalamus, medulla, midbrain, thalamus, pons, and hippocampus. These data, using a rat CRF ligand homologous to the endogenous peptide, are consistent with those from previous studies demonstrating the presence of specific binding sites for ovine CRF in rat brain, and provide further support for the suggestion that endogenous CRF may function as a neurotransmitter in the CNS.

show abstract

“…In brain slice preparations CRF produces postsynaptic depolarization in most of amygdala cells (Eberly et al, 1983;Rainnie et al, 1992) but presynaptic inhibitory effects on CRF-IR neurons have also been proposed (Wiersma et al, 1993). CRF binding sites are located on the perikarya, dendrites, and terminals of peptide-containing medium spiny neurons of the Ce, including CRF-IR neurons.…”

Section: Discussionmentioning

confidence: 99%

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

et al. 1995

View full text Add to dashboard Cite

Previous research has suggested a role for corticotropin-releasing factor (CRF) in the anxiogenic effects of stressful stimuli and ethanol withdrawal. This hypothesis was explored in a series of experiments using intracranial microdialysis to monitor CRF-like immunoreactivity (CRF-IR) in the extracellular compartment of the rat amygdala. The synaptic origin of CRF-IR release in the amygdala was determined in vitro by assessing the Ca2+ dependency of 4-aminopyridine stimulated CRF-IR release from tissue preparations of rat amygdala. In vivo experiments were performed in awake rats after the placement of microdialysis probes in the amygdala. In the first experiment, transient restraint stress (20 min) produced an increase of CRF-IR release (basal levels, 1.19 +/- 0.15 fmol/50 microliters; stress levels, 4.54 +/- 1.33 fmol/50 microliters; p < 0.05) that returned to basal values within 1 hr. When 4-aminopyridine (5 mM) was added to the perfusion medium, it consistently increased CRF-IR release (4.83 +/- 0.92 fmol/50 microliters, p < 0.05). In the second experiment, CRF-IR release was measured during ethanol withdrawal in rats previously maintained for 2–3 weeks on a liquid diet containing ethanol (8.5%). Basal CRF-IR levels were 2.10 +/- 0.43 fmol/50 microliters in ethanol exposed rats and 1.30 +/- 0.19 fmol/50 microliters in control rats. During withdrawal, a progressive increase of CRF-IR levels over time was observed, reaching peak values at 10–12 hr after the onset of withdrawal (10.65 +/- 0.49 fmol/50 microliters vs 1.15 +/- 0.30 fmol/50 microliters of control rats, p < 0.01).

show abstract

Iontophoretic mapping of corticotropin-releasing factor (CRF) sensitive neurons in the rat forebrain

Cited by 83 publications

References 18 publications

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

Corticotropin-releasing factor receptors in the rat central nervous system: characterization and regional distribution

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

Contact Info

Product

Resources

About