Corticotropin-Releasing Factor Disrupts Sensory Responses of Brain Noradrenergic Neurons

Abstract

In order to elucidate the possible role of noradrenergic neurons of the nucleus locus coeruleus (LC) in stress responses, the effects of corticotropin-releasing factor (CRF) on LC neuronal activity were characterized. In halothane-anesthetized rats, intracerebroventricular administration of CRF was found to have two distinct actions: (1) A dose-dependent increase in spontaneous discharge activity was observed 3 min after peptide injection, with 1.0 and 3.0 µg CRF increasing activity by 7 ± 2 and 47 ± 12%, respectively; Ala¹⁴CRF (3.0 µg), an inactive analogue of CRF, had no effect on LC spontaneous discharge rates. These results confirm and extend previous studies of CRF activation of LC basal discharge activity; (2) additionally, CRF (1.0 and 3.0 µg) disrupted sensory responses of LC cells to sciatic nerve stimulation. As previously reported, responses of LC neurons to electrical stimulation of the sciatic nerve usually consisted of a brief activation beginning 20–40 ms after stimulus followed by a period of relatively suppressed activity lasting 100–200 ms. CRF attenuated both components. Responses plotted as normalized, cumulative histograms became more linear in the presence of CRF (1.0 and 3.0 µg), suggesting that discharge rates during phasic responses to sciatic stimulation were similar to spontaneous rates. Statistical comparison using the Kolmogorov-Smirnoff test or correlation coefficients demonstrated that both 1.0 and 3.0 µg CRF reduced response components, while 0.3 µg CRF and Ala¹⁴CRF (3.0 µg) had no effect. The degree of attenuation of LC sensory responses by CRF was not linearly related to the magnitude of CRF-in-duced increases in spontaneous discharge rate, suggesting that these are distinct effects of CRF. These actions of CRF on LC activity may represent an important mechanism in the central mediation of stress responses.

Effects ofGlycyrrhizae Radixon Repeated Restraint Stress-induced Neurochemical and Behavioral Responses

“…The LC is considered a crucial site for the CNS stress response. An abundance of data collected using different techniques has shown that corticotropin releasing hormone can modulate the rate of discharge of NE and TH in LC neurons [28][29][30]. In this study, the repeated restraint stress caused a 35.0% increase in the TH-ir cells in the LC.…”

Impact of overactive bladder on the brain: Central sequelae of a visceral pathology

“…Bladder pressure was recorded simultaneously with neuronal activity. To determine whether bladder obstruction altered LC responses to sensory stimuli, we recorded neuronal responses to repeated sciatic nerve stimulation (1 mA, 0.5 ms, 0.5 Hz, 60 trials) as peristimulus time histograms (PSTHs) (39). When more than one cell was recorded in one LC, these were all in the same dorsal-ventral track, and the depth of each recording was noted for later verification of cellular location.…”

“…Discharge rates before and during bladder distention were compared by using the Student's paired t test. PSTHs were analyzed as described elsewhere (39). All t tests were two-tailed, with P Ͻ 0.05 being deemed statistically significant.…”

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

“…CRF administration, i.c.v. and site-specifically, alters the firing of NE and 5-HT neurons (Kirby et al 2000;Price et al 1998;Valentino and Foote 1987), and modulates neurotransmitter release at their respective terminal fields de Groote et al 2005;Price and Lucki 2001). Evocation of anxiety responses by CRF infusion is accompanied by concomitant changes in forebrain 5-HT (Kagamiishi et al 2003) and NE transmission.…”