Journal of Neuroscience, Vol 8, 1016-1025, Copyright © 1988 by Society for Neuroscience
Corticotropin-releasing hormone increases tonic but not sensory-evoked activity of noradrenergic locus coeruleus neurons in unanesthetized rats
RJ Valentino and SL Foote
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
These studies were designed to further test the hypothesis that
corticotropin-releasing hormone (CRH) is released from axons innervating
the noradrenergic neurons of the locus coeruleus (LC) and serves to
activate these neurons during stress responses. Specifically, the effects
of exogenous CRH on the electrophysiological activity of LC neurons in
unanesthetized rats were characterized. Intracerebroventricular (I.C.V.)
injection of CRH (0.3-3.0 micrograms) caused a dose-dependent increase in
LC spontaneous discharge rates that became statistically significant 6-9
min after injection and was still evident 30-40 min later. A 1.0 and 3.0
micrograms amount of CRH caused peak increases of 86 +/- 32% and 184 +/-
29% (SEM), respectively. In contrast, neither the lowest dose of CRH (0.3
microgram) nor a high dose of Ala 14CRH (3.0 micrograms), an inactive
analog of CRH, altered LC spontaneous activity. The effects of CRH
administration on sensory- evoked activity of LC neurons were also
determined. As previously reported (Foote et al., 1980; Aston-Jones and
Bloom, 1981b), the repeated presentation of auditory tone stimuli resulted
in a brief enhancement of LC discharge, which was usually followed by a
period of relatively decreased activity. Administration of 1.0 or 3.0
micrograms CRH enhanced basal discharge during sensory testing, but
discharge rates during the excitatory component of the sensory response
were not altered. Quantitative analyses revealed that these doses of CRH
produced a statistically significant decrease in the ratio of sensory-
evoked to basal discharge rates. Additional analyses of the temporal
distribution of discharge activity for individual recording sites during
sensory testing demonstrated that 1.0 and 3.0 micrograms CRH altered
relative response magnitudes to a statistically significant extent in 7 of
10 and 5 of 7 cases, respectively, while 0.3 microgram CRH and 3.0
micrograms Ala 14CRH were without effect. The present results are
consistent with previous studies of CRH effects on LC activity in
anesthetized rats (Valentino et al., 1983; Valentino and Foote, 1987).
However, in unanesthetized animals, CRH is more potent in increasing tonic
activity and does not decrease the absolute magnitude of sensory-evoked
activity. The present results support the hypothesis that CRH released from
fibers innervating the LC may affect the tonic activity of these cells and
the relationship between tonic discharge and phasic, sensory-evoked
activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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