Increased risk-taking behavior in dopamine transporter knockdown mice: further support for a mouse model of mania

• Published in: Journal of psychopharmacology (Oxford) 2011-07, Vol.25 (7), p.934-943
• Main Authors: Young, Jared W, van Enkhuizen, Jordy, Winstanley, Catharine A, Geyer, Mark A
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Affective disorders; Animals; Behavior; Behavior, Animal; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - genetics; Bipolar Disorder - metabolism; Bipolar Disorder - psychology; Conditioning, Operant; Disease Models, Animal; Dopamine; Dopamine Plasma Membrane Transport Proteins - deficiency; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine transporter; Exploration; Exploratory Behavior; Female; Gambling; Genotype; Mania; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mood disorders; Motor Activity - genetics; Neuropharmacology; Pharmacology. Drug treatments; Phenotype; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk taking; Rodents; Time Factors
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881111400646

Reduced functioning of the dopamine transporter (DAT) has been linked to bipolar disorder (BD). Mice with reduced DAT functioning (knockdown, KD) exhibit a behavioral profile in the mouse Behavioral Pattern Monitor (BPM) consistent with patients with BD mania in the human BPM. Patients with BD also exhibit increased risk taking, which can be quantified using the Iowa Gambling Task (IGT). We hypothesized that DAT KD mice would exhibit increased risk-taking behavior in a novel mouse version of the IGT. DAT KD and wildtype (WT) littermates were trained in the mouse IGT. In session 1, KD mice initially made riskier choices, but later performed comparably to WT mice. Once trained to stable choice performance, DAT KD mice continued to exhibit a trend to choose the riskier options more than WT mice. Finally, we confirmed that these DAT KD mice also exhibited an exploratory profile in the BPM consistent with patients with BD mania, where risky choice behavior modestly correlated with specific exploration. These data demonstrate that DAT KD mice chose the riskier options more than WT mice, providing further support for the use of DAT KD mice as a model of BD mania.