CRH receptors

CRH and its receptors have generated increasing interest as a target for medications. In addition to the pituitary, CRH receptors have been localized to the cortex, the nuclei of the amygdala, the LC, and regions of the hypothalamus. It has also been reported that CRH increases LC activity, and that local injection of CRH into the LC increases behavioral responses consistent with increased anxiety [105]. Furthermore, CRH antagonists have been repeatedly shown to have anxiolytic effects in animal models. 

CRHR1/CRHR2 Double Knockout Life Without CRH Receptors. 129... 

Keywords CRH CRF Depression Anxiety CRH receptor antagonist R121919 ... 

NBI 30775 CRH receptor type 1 CRH receptor type 2 Transgenic mice ... 

Weninger SC, Dunn AJ, Muglia LJ, Dikkes P, Miczek KA, Swiergiel AH, Berridge C W, Ma-jzoub JA (1999) Stress-induced behaviors require the corticotropin-releasing hormone (CRH) receptor, but not CRH. Proc Natl Acad Sci USA 96 8283-8288... 

Fig. 1 Effects of forced swimming (15 min, water temperature 25 °C) on hippocampal extracellular levels of 5-HT (expressed as percentage of baseline) in male Wistar rats as assessed by in vivo microdialysis. Extracellular levels of 5-HT showed a dramatic increase in rats that dived diming the forced swimming procedure. This effect could be prevented by i.c.v. pretreatment of the rats with the CRH receptor antagonist o-Phe-CRH 12-41 (5 pg)., p<0.05 as compared to non-divingsaline-pretreated rats , p<0.05 as compared to diving d-Phe-CRHi2-4i -treated rats (Scheffe post-hoc comparisons). For experimental details, please see text and original paper. (From Linthorst et al. 2002, with permission of European Journal of Neuroscience)...

Taken together, the data reviewed here show that forced swim stress induces a highly differentiated (putatively CRH-dependent) response in serotoniner-gic neurotransmission in higher brain structures, with the final outcome of the manipulation depending on the exact experimental design. Moreover, the dramatic CRH receptor-dependent increase in hippocampal 5-HT as observed... 

There is extensive evidence consistent with a role for CRH in mediating stress effects on memory consohdation. Activation of CRH receptors in the BLA by CRH released from the CEA facilitates stress effects on memory consohdation. Memory enhancement produced by CRH infusions in the hippocampus are blocked by propranolol, suggesting CRH, through a presynaptic mechanism, stimulates NE release in the hippocampus (Roozendaal et al. 2002). 

Other hand, the locus coeruleus is known to be richly innervated with CRH im-munoreactive fibers (Valentino et al. 1993). Stress- or CRH-induced increases in locus coeruleus neuronal firing are blocked by CRH receptor antagonists and chronic antidepressant treatment (e.g., Valentino et al. 1990 Schulz et al. 1996), suggesting that anxiogenic effects of CRH are mediated through its actions on the locus coeruleus noradrenergic system (Butler et al. 1990). 

Zwanzger et al. 2003). Administration of the neuropeptide ANP was effective in reducing the CCK-4-elicited panic reaction in patients with panic disorder and to a lesser extent in healthy controls. Moreover, ANP inhibited the CCK-4-induced rise of ACTH in both patients and controls, which may be attributed to a reduced hypothalamic CRH release (Jessop 1999 Wiedemann et al. 2001). Interestingly, ACTH release in response to CCK-4 was foimd to be blunted in patients when compared to healthy controls. This finding is possibly due to a chronic hypersecretion of CRH with a subsequent downregulation of CRH receptors in such patients (Wiedemann et al. 2001). 

An enhanced level of corticotropin-releasing hormone (CRH) receptors is found in the central amygdala of rat mothers who spend relatively less time licking and grooming offspring (Francis et ah, 1999a), this... 

FICURE 1-1. Intracerebral infusion of antisense oligonucleotides (AS-ODN) that were targeted to the cloned CRH, and CRH2 receptor mRNA prevent translation into the receptor protein. Only a knock-down of the CRH, receptor, but not of the CRH2 receptor, reduces anxiety-related behavior in rats that were exposed to the elevated plus-maze test after central corticotropin-releasing hormone (CRH) administration. P <. 05, P <. 01. 

Source. Adapted from Liebsch G, Landgraf R, Gerstberger R, et al Chronic Infusion of a CRH, Receptor Antisense OMgodeoxynucleotide Into the Central Nucleus of the Amygdala Reduced Anxiety-Related Behavior in Socially Defeated Rats. Regulatory Peptides 59 229-239, 1995. Copyright 1995, Elsevier Science - NL. Used with permission. Data also from Skutella et al. 1994. 

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