title: Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior.
abstract: Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to affective disorders such as anxiety and depression. Dampening HPA activity has, therefore, been considered as a possible means of treating affective disorders. Given the important role of vasopressin in modulating the HPA axis, one strategy has focused on inhibiting activity of the vasopressin 1b (V1b) receptor. In animals, V1b receptor antagonists reduce plasma stress hormone levels and have been shown to have an anxiolytic-like effect. Recently, V1B-30N was identified as a highly potent V1b receptor antagonist with selectivity over other vasopressin receptors, which is evaluated here in rodent models of anxiety-like and depression-like behaviors. V1B-30N (1-30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in rat pups without producing any sedative effects in the animals. Similarly, V1B-30N (3-30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in guinea pig pups. In a conflict assay, conditioned lick suppression, V1B-30N (3-30mg/kg, IP) increased punished licking. To assess antidepressive-like properties, V1B-30N (1-30mg/kg) was tested in the mouse and rat forced-swim tests but was found to be inactive. These results are consistent with previous findings with other V1b antagonists, which suggest that acute pharmacological antagonism of the V1b receptor has anxiolytic-like but not antidepressant-like properties.
authors.affiliation: Departments of In Vivo Pharmacology, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA. Electronic address: Robert.Hodgson@Merck.com.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hodgson
authors.affiliation: Departments of Neuroscience, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Deborra
authors.initials: D
authors.lastname: Mullins
authors.affiliation: Departments of Neuroscience, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Sherry X
authors.initials: SX
authors.lastname: Lu
authors.affiliation: Departments of Neuroscience, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Guzzi
authors.affiliation: Departments of Neuroscience, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Departments of In Vivo Pharmacology, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Carina J
authors.initials: CJ
authors.lastname: Bleickardt
authors.affiliation: Departments of Medicinal Chemistry, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Jack D
authors.initials: JD
authors.lastname: Scott
authors.affiliation: Departments of Medicinal Chemistry, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Miller
authors.affiliation: Departments of Medicinal Chemistry, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stamford
authors.affiliation: Departments of Neuroscience, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Parker
authors.affiliation: Departments of In Vivo Pharmacology, Merck and Co. Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Geoffrey B
authors.initials: GB
authors.lastname: Varty
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism*; D013550:Swimming; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin
keywords: Anxiety; Depression; Mouse; Rat; V(1b) receptor; Vasopressin