[Neurobiology and genetics of anxiety in an animal model].
This paper presents a valid animal model of innate anxiety/depression: anxious (HAB) or non-anxious (LAB) rats, which show stable and robust responses in a variety of ethological tests. In addition to their extreme anxiety-related behavior, HAB animals are characterized by passive stress coping, an activated stress (HPA) axis, and increased stress vulnerability. The enhanced expression and release of arginine vasopressin (AVP) in the hypothalamus of HAB rats seem to underlie these phenomena. Accordingly, an AVP receptor antagonist attenuates anxiety-related behavior and normalizes the HPA axis and the dexamethasone/CRH test. Treatment with the antidepressive drug paroxetine reduces the overexpression of AVP and normalizes both the depression-like behavior and neuroendocrine correlates of anxiety/depression. The complex phenotyping led us to the conclusion that the AVP gene is likely to be a candidate gene of inborn anxiety. Partial genotyping of HAB animals results in the identification of polymorphisms (SNPs) in the promoter domain of the AVP gene, thus potentially leading to novel strategies of diagnosis and therapy of anxiety disorders and depression.
Landgraf
R
R
Max-Planck-Institut für Psychiatrie, Munich.
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001007:Anxiety / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001127:Arginine Vasopressin / Q000235:genetics* / Q000502:physiology; D001143:Arousal / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone; D003863:Depression / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D003907:Dexamethasone; D004195:Disease Models, Animal; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017374:Paroxetine / Q000494:pharmacology; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D011919:Rats, Inbred Strains; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000235:genetics* / Q000502:physiology
D018687:Antidepressive Agents, Second-Generation; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D017374:Paroxetine; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone