Corticotropin-releasing factor immunoreactivity is widely distributed within the central nervous system of the rat: an immunohistochemical study

Abstract

The discovery of a 41-amino acid peptide with potent corticotropin-releasing factor properties has prompted a search for neurons that contain this substance and potentially utilize it in intercellular communication. The present study utilized immunohistochemical methods and an antiserum directed against a synthetic replica of ovine corticotropin-releasing factor. The rat hypothalamus was found to contain striking immunoreactive groups of neuronal perikarya within the paraventricular, periventricular, and anterior hypothalamic nuclei, some of which are likely to project to the external layer of the median eminence and thereby comprise a hypophysiotropic system. Certain other hypothalamic nuclei, as well as many other regions of the central nervous system, were found to contain corticotropin-releasing factor-immunoreactive neurons. Among the most prominent of these were neurons in the bed nucleus of stria terminalis, the central nucleus of the amygdala, the region of the dorsal raphe, locus ceruleus, the external cuneate nucleus, and the medullary reticular formation. Thus, corticotropin-releasing factor, like many other neurohormones and peptides, may participate in neuroendocrine regulation as well as play a role as a neurotransmitter-like substance in numerous extrahypothalamic circuits.

Buprenorphine and a CRF1 Antagonist Block the Acquisition of Opiate Withdrawal-Induced Conditioned Place Aversion in Rats

“…Microinjections into the central nucleus of the amygdala of lower doses of the CRF antagonist also reversed the anxiogenic-like effects of alcohol withdrawal (Rassnick et al, 1993), and similar doses of the CRF antagonist injected into the amygdala were active in reversing opiate-induced conditioned place aversion (Heinrichs et al, 1995). Studies using in vivo microdialysis have shown that rats withdrawn from chronic alcohol, withdrawn from chronic cocaine, and precipitously withdrawn from chronic cannabinoids show increases in the release of CRF from the central nucleus of the amygdala (Cummings et al, 1983;Merlo-Pich et al, 1995;Rodriguez de Fonseca et al, 1997). Particularly intriguing are recent studies demonstrating a role for norepinephrine in the bed nucleus of the stria terminalis in the conditioned place aversions associated with opiate withdrawal (Delfs et al, 2000).…”

Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for Math1

“…Together with the adjacent norepinephrine (NE) neurons of the locus coeruleus (LC, A6), these NO neurons, which coexpress acetylcholine (4,35), constitute an important component of the reticular activating system (RAS) vital for arousal. Likewise, CRH neurons in the PPTg and in Barrington's nucleus (BN), located immediately adjacent to the LDT and LC (36), are also Math1-dependent. The BN contains the largest group of CRH neurons in the hindbrain, responds to the interoceptive inputs of bladder and colon distension, and projects to the LC to increase the activity of NE neurons and stimulate arousal (37)(38)(39).…”

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

“…Post et al, 1981;Charney et al, 1993), such effects might be amplified by stress-induced kindling of various limbic areas, including the amygdala and BNST. The amygdala and BNST show particularly dense concentrations of CRH cell bodies and receptors (Cummings et al, 1983;De Souza et al, 1984;Sawchenko and Swanson, 1985;Sakanaka et al, 1987;Chalmers et al, 1995;Lovenberg et al, 1995), and chronic stress increased CRH mRNA in the CeA and BNST (Mamalaki et al, 1992;Makino et al, 1994aMakino et al, ,b, 1995. Taken together, these data raise the possibility that stress may sensitize CRH systems in limbic structures, such as the amygdala and/or BNST, leading to a persistent increase in CRH transmission.…”