Alterations in Central Neuropeptide Expression, Release, and Receptor Binding in Rats Bred for High Anxiety: Critical Role of Vasopressin

Universität Regensburg, Ratisbon, Bavaria, Germany
Neuropsychopharmacology (Impact Factor: 7.05). 02/2004; 29(1):1-14. DOI: 10.1038/sj.npp.1300290
Source: PubMed


To model aspects of trait anxiety/depression, Wistar rats were bred for extremes in either hyper (HAB)- or hypo(LAB)-anxiety as measured on the elevated plus-maze and in a variety of additional behavioral tests. Similar to psychiatric patients, HAB rats prefer passive stress-coping strategies, indicative of depression-like behavior, show hyper-reactivity of the hypothalamo-pituitary-adrenal axis, and a pathological response to the dexamethasone/corticotropin-releasing hormone (CRH) challenge test. Here we tested central mRNA expression, release patterns, and receptor binding of neuropeptides critically involved in the regulation of both anxiety-related behavior and the HPA axis. Thus, CRH, arginine-8-vasopressin (AVP), and oxytocin (OXT) were studied in brains of HAB and LAB males both under basal conditions and after exposure to a mild emotional stressor. In HAB rats, CRH mRNA was decreased in the bed nucleus of the stria terminalis only. While no significant difference in CRH1-receptor binding was found in any brain area, CRH2-receptor binding was elevated in the hypothalamic paraventricular nucleus (PVN), the ventromedial hypothalamus, and the central amygdala of HABs compared to LABs. AVP, but not OXT, mRNA expression as well as release of the neuropeptide, were higher in the PVN of HABs, whereas AVP V1a-receptor binding failed to show significant differences in any brain region studied. Remarkably, intra-PVN treatment of HABs with the AVP V1-receptor antagonist d (CH(2))(5) Tyr (Me) AVP resulted in a decrease in anxiety/depression-related behavior. The elevated expression and release of AVP within the PVN of HAB rats together with the behavioral effects of the AVP V1-receptor antagonist suggest a critical involvement of this neuropeptide in neuroendocrine and behavioral phenomena associated with trait anxiety/depression.

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Available from: Paul M Plotsky, Apr 02, 2014
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    • "Peptides that have been used in this way include analogs of ovine CRF (Perrin et al., 1986), rat Ucn 1 (Perrin et al., 1999), and PS-Svg (Chen et al., 2005) as well as the antagonists, astressin (Gulyas et al., 1995; Rivier and Rivier, 2014) and antisauvagine-30 (Ruhmann et al., 1998). Of these, radioiodinated analogs of PS-Svg, such as [Tyr 0 -Glu 1 , Nle 17 ]- PS-Svg and [Tyr 0 ]-PS-Svg, which bind both CRF receptors with relatively high affinity, have come to be most widely used in pharmacological and functional studies (Grigoriadis et al., 1996; Primus et al., 1997; Rominger et al., 1998; Ruhmann et al., 1998; Ardati et al., 1999; Sanchez et al., 1999; Skelton et al., 2000; Bakshi et al., 2002; Lawrence et al., 2002; Maillot et al., 2003; Wigger et al., 2004; Gehlert et al., 2005; Lim et al., 2005; Waser et al., 2006; Silberstein et al., 2009). "
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