Anxiety vasopressin

Cholecystokinin (CCK) is produced in the intestine and the brain. It appears to be an important mediator of anxiety. It also stimulates vasopressin secretion and slows gastric emptying. In addition, it is an important humoral satiety signal (appetite control). Various antagonists have been developed and are currently being investigated with regard to their therapeutic potential. 

Bale TL, Contarino A, Smith GW, Chan R, Gold LH, Sawchenko PE, Koob GF, Vale WW, Lee KF (2000) Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet 24 410-414 Bale TL, Picetti R, Contarino A, Koob GF, Vale WW, Lee KF (2002) Mice deficient for both corticotropin-releasing factor receptor 1 (CRFRl) and CRFR2 have an impaired stress response and display dichotomous anxiety-like behavior. J Neurosci 22 193-199 Barberis C, Tribollet M (1996) Vasopressin and oxytocin receptors in the central nervous system. Grit RevNeurobiol 10 119-154... 

Landgraf R, Gerstberger R, Montkowski A, Probst JC, Wotjak CT, Holsboer F, Engelmann M (1995) VI vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neimosci 15 4250-4258... 

Liebsch G, Wotjak CT, Landgraf R, Engelmann M (1996) Septal vasopressin modulates anxiety-related behaviour in rats. Neurosci Lett 217 101-104... 

Fig. 2 Increased synthesis, content and release of vasopressin (AVP) in the PVN of high-anxiety (HAB) vs low-anxiety (LAB) rats under basal circumstances. Above left in situ hybridization. Above right immunocytochemistry (courtesy of Dr. N. Singewald, University of Innsbruck). Middle and below intra-PVN release of AVP and oxytocin (OXT) measured by in vivo microdialysis under basal conditions and in response to hypertonic stimulation to reveal the releasable neuropeptide pool. p<0.05, p<0.01 vs LAB. (Adapted from Wigger et al. 2004)...

Altemus M, Cizza G, Gold P (1992) Chronic fluoxetine treatment reduces hypothalamic vasopressin secretion in vitro. Brain Res 593 311-313 Appenrodt E, Schnabel R, Schwarzberg H (1998) Vasopressin administration modulates anxiety-related behavior in rats. Physiol Behav 64 543-547 Arborelius L, Owens MJ, PlotskyPM, Nemeroff CB (1999) The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol 160 1-12 Argiolas A, Gessa GL (1991) Central functions of oxytocin. Neurosci Biobehav Rev 15 217-231... 

Liebsch G, Wotjak CT, Landgraf R, Engelmann M (1996) Septal vasopressin modulates anxiety-related behavioim in rats. Neurosci Lett 217 101-104 Liebsch G, Landgraf R, Engelmann M, Lorscher P, Holsboer F (1999) Differential behavioural effects of chronic infusion of CRH 1 and CRH 2 receptor antisense oligonucleotides into the rat brain. J Psychiatr Res 33 153-163... 

Ron an PJ, Kramer GL, Petty F (2001) Corticotropin releasing factor and arginine vasopressin effects in the learned helplessness animal model. Soc Neurosci Meeting Abstr 414.20 Rosen JB, Schulkin J (1998) From normal fear to pathological anxiety. Psychol Rev 105 325-350... 

Wigger A, Sanchez MM, Mathys KC, Ebner K, Liu D, Kresse A, Neumann ID, Holsboer F, Plotsky PM, Landgraf R (2004) Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety critical role of vasopressin. Neimopsy-chopharmacology 29 1 -14... 

The nonapeptide vasopressin (AVP) is synthesized in the paraventricular nucleus of the hypothalamus (PVN) and the nucleus supraopticus. Besides its role in fluid regulation, AVP is also a key modulator of the HPA system, where it potentiates the effects of CRH on adrenocorticotropic hormone (ACTH) release. Extrahypothalamic AVP-containing neurons are localized in the medial amygdala and the bed nucleus of the stria terminalis. AVP applied intracere-broventricularly or to the lateral septum has been shown to affect cognition, social behavior, and anxiety-like behavior in rodents (Insel et al. 2001). 

CRH probably does not act alone. According to clinical neuroendocrinology, vasopressin is a prime candidate for the synergy of CRH effects at pituitary CRHj receptors, and it also has behavioral effects that are compatible with a role in depression. Chronic psychosocial stress enhances vasopressin expression and increases the number of hypothalamic neurons coexpressing CRH and vasopressin. Infusion of an antisense oligodeoxy-nucleotide, which corresponds to the mRNA of vasopressin type 1 receptor, into the septum led to reduced anxiety-related behavior that parallels decreases in vasopressin receptor binding (Landgraf et al. 1995). 

Physical and mental stress influence the concentrations of many plasma constituents. Anxiety stimulates increased secretion of aldosterone, angiotensin, catecholamines, cortisol, prolactin, renin, somatotropin, TSH, and vasopressin. Plasma concentrations of albumin, cholesterol, fibrinogen, glucose, insulin, and lactate also increase. 

Indeed, previous studies on animal models have demonstrated the critical role of QT and the related peptide vasopressin (VP) in stress, coping responses and social, adaptive behaviours influencing social affiliation and social recognition, sexual and maternal behaviours and anxiety and reactivity to stressors (Carter and Keverne, 2002 Pedersen and Boccia, 2006). 

Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ (2004) Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin Vla receptor knockout mice. Neuropsychopharmacology 29 483 93. 

Appenrodt E, Schnabel R, Schwarzberg H (1998) Vasopressin administration modulates anxiety-related behavior in rats. Physiol Behav 64 543-547. 

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