title: Vasopressin in health and disease with a focus on affective disorders.
abstract: The therapies of mood and anxiety disorders are not solved, because current antidepressants have delayed onset of therapeutic action and a significant number of patients are non-responsive. Research on the field was leaning towards neuropeptides as therapeutic targets. Vasopressin (VP) is a hot candidate, as beyond its peripheral actions VP is implicated in interneuronal communication and modulates the hypothalamo-pituitary-adrenal (HPA), the key stress axis, as well as behavioural functions. Affective disorders are stress related disorders and the most frequently occurring abnormality in depressed subjects is hyperactivity of the HPA. VP with nucleus paraventricularis hypothalami origin is a direct adrenocorticotrophin secretagogue through its V1b receptor. VP seems to have special importance under prolonged stress conditions, which are known to be strong predictive factor of depressive disorder and can induce depressive-like symptoms. Preclinical and clinical data summarized in this review underline the importance of VP in the development of anxiety- and depressive-like symptoms. Orally active nonpeptiderg V1b antagonists were developed and seemed to have effective anxiolytic and antidepressant profile in preclinical studies, which was not fully confirmed by clinical observations. It seems that V1a receptors on special brain areas could have same importance. Taken together current knowledge strongly implies an importance of vasopressinergic regulation in affective disorders and consider VP as endogenous anxiogenic/depressogenic substance. However, wide range of side effects could develop as a result of an intervention on the VP system; therefore there is a need for area-specific targeting of VP receptors (e.g. with modified nanoparticles).
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Szigony 43, Hungary. zelena.dora@koki.hu
authors.forename: Dóra
authors.initials: D
authors.lastname: Zelena
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D065092:Antidiuretic Hormone Receptor Antagonists; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D003919:Diabetes Insipidus / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007177:Inappropriate ADH Syndrome / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D019964:Mood Disorders / Q000188:drug therapy / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011910:Rats, Brattleboro; D011922:Rats, Mutant Strains; D017483:Receptors, Vasopressin / Q000145:classification / Q000187:drug effects; D013315:Stress, Psychological / Q000503:physiopathology; D014667:Vasopressins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D014667:Vasopressins