title: Investigating the underlying mechanisms of aberrant behaviors in bipolar disorder from patients to models: Rodent and human studies.
abstract: Psychiatric patients with bipolar disorder suffer from states of depression and mania, during which a variety of symptoms are present. Current treatments are limited and neurocognitive deficits in particular often remain untreated. Targeted therapies based on the biological mechanisms of bipolar disorder could fill this gap and benefit patients and their families. Developing targeted therapies would benefit from appropriate animal models which are challenging to establish, but remain a vital tool. In this review, we summarize approaches to create a valid model relevant to bipolar disorder. We focus on studies that use translational tests of multivariate exploratory behavior, sensorimotor gating, decision-making under risk, and attentional functioning to discover profiles that are consistent between patients and rodent models. Using this battery of translational tests, similar behavior profiles in bipolar mania patients and mice with reduced dopamine transporter activity have been identified. Future investigations should combine other animal models that are biologically relevant to the neuropsychiatric disorder with translational behavioral assessment as outlined here. This methodology can be utilized to develop novel targeted therapies that relieve symptoms for more patients without common side effects caused by current treatments.
authors: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA 92093-0804, United States; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors: Jordy
authors: J
authors: van Enkhuizen
authors: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA 92093-0804, United States; Research Service, VA San Diego Healthcare System, San Diego, CA, United States. Electronic address: mgeyer@ucsd.edu.
authors: Mark A
authors: MA
authors: Geyer
authors: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA 92093-0804, United States.
authors: Arpi
authors: A
authors: Minassian
authors: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA 92093-0804, United States.
authors: William
authors: W
authors: Perry
authors: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA 92093-0804, United States.
authors: Brook L
authors: BL
authors: Henry
authors: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA 92093-0804, United States; Research Service, VA San Diego Healthcare System, San Diego, CA, United States.
authors: Jared W
authors: JW
authors: Young
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D006801:Humans; D009043:Motor Activity; D055139:Sensory Gating; D057170:Translational Research, Biomedical
keywords: Animal model; Bipolar disorder; Dopamine transporter; Translational