1. ¹Max Planck Institute of Psychiatry, Behavioural Neuroendocrinology, Munich, Germany
2. ²Emory University School of Medicine, Atlanta, USA
3. ³University of Innsbruck, Innsbruck, Austria
4. ⁴Karl-Franzens-University Graz, Graz, Austria
5. ⁵University of Regensburg, Regensburg, Germany

Correspondence: Dr A Wigger, Max Planck Institute of Psychiatry, Kraepelinstr. 2, D 80804 Munich, Germany. Tel: +49 89 30622 228; Fax: +49 89 30622 569; E-mail: Wigger@mpipsykl.mpg.de

Received 4 March 2003; Revised 10 June 2003; Accepted 15 July 2003; Published online 27 August 2003.

Abstract

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 (CH₂)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.