Dopamine transporter knockdown mice in the behavioral pattern monitor: A robust, reproducible model for mania-relevant behaviors

2019 ◽  
Vol 178 ◽  
pp. 42-50 ◽  
Author(s):  
Molly A. Kwiatkowski ◽  
Gerhard Hellemann ◽  
Catherine A. Sugar ◽  
Zackary A. Cope ◽  
Arpi Minassian ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Behavioral Pattern ◽  
Behavioral Pattern Monitor

scholarly journals Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels

2017 ◽  
Vol 31 (10) ◽  
pp. 1334-1346 ◽  
Author(s):  
Morgane Milienne-Petiot ◽  
Lucianne Groenink ◽  
Arpi Minassian ◽  
Jared W Young
Keyword(s):  
Bipolar Disorder ◽  
Dopamine Transporter ◽  
Risk Taking ◽  
Iowa Gambling Task ◽  
Sch 23390 ◽  
Progressive Ratio ◽  
Behavioral Pattern ◽  
Wild Type ◽  
Wild Type Littermate ◽  
Behavioral Pattern Monitor

Background: Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D1-family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Methods: Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D1-family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Results: Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Conclusions: Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D1-family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D1-family receptors supports the hypothesis that D1 and/or D5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

scholarly journals Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor

2016 ◽  
Vol 240 ◽  
pp. 278-283 ◽  
Author(s):  
William Perry ◽  
Meghan McIlwain ◽  
Karen Kloezeman ◽  
Brook L. Henry ◽  
Arpi Minassian
Keyword(s):  
Behavioral Pattern ◽  
Behavioral Pattern Monitor

scholarly journals Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e24185 ◽  
Author(s):  
Arpi Minassian ◽  
Brook L. Henry ◽  
Jared W. Young ◽  
Virginia Masten ◽  
Mark A. Geyer ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Behavioral Pattern ◽  
Novelty Seeking ◽  
Healthy Individuals ◽  
Behavioral Pattern Monitor ◽  
Repeated Assessment

scholarly journals Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice

2010 ◽  
Vol 25 (11) ◽  
pp. 1548-1561 ◽  
Author(s):  
Adam L Halberstadt ◽  
Liselore Koedood ◽  
Susan B Powell ◽  
Mark A Geyer
Keyword(s):  
Serotonin Receptor ◽  
Gene Deletion ◽  
Therapeutic Agent ◽  
Receptor Gene ◽  
Behavioral Pattern ◽  
Behavioral Effects ◽  
Receptor Subtypes ◽  
Potential Therapeutic Agent ◽  
Way 100635 ◽  
Behavioral Pattern Monitor

Psilocin (4-hydroxy- N, N-dimethyltryptamine) is a hallucinogen that acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors. Psilocin is the active metabolite of psilocybin, a hallucinogen that is currently being investigated clinically as a potential therapeutic agent. In the present investigation, we used a combination of genetic and pharmacological approaches to identify the serotonin (5-HT) receptor subtypes responsible for mediating the effects of psilocin on head twitch response (HTR) and the behavioral pattern monitor (BPM) in C57BL/6J mice. We also compared the effects of psilocin with those of the putative 5-HT2C receptor-selective agonist 1-methylpsilocin and the hallucinogen and non-selective serotonin receptor agonist 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT). Psilocin, 1-methylpsilocin, and 5-MeO-DMT induced the HTR, effects that were absent in mice lacking the 5-HT2A receptor gene. When tested in the BPM, psilocin decreased locomotor activity, holepoking, and time spent in the center of the chamber, effects that were blocked by the selective 5-HT1A antagonist WAY-100635 but were not altered by the selective 5-HT2C antagonist SB 242,084 or by 5-HT2A receptor gene deletion. 5-MeO-DMT produced similar effects when tested in the BPM, and the action of 5-MeO-DMT was significantly attenuated by WAY-100635. Psilocin and 5-MeO-DMT also decreased the linearity of locomotor paths, effects that were mediated by 5-HT2C and 5-HT1A receptors, respectively. In contrast to psilocin and 5-MeO-DMT, 1-methylpsilocin (0.6–9.6 mg/kg) was completely inactive in the BPM. These findings confirm that psilocin acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors in mice, whereas the behavioral effects of 1-methylpsilocin indicate that this compound is acting at 5-HT2A sites but is inactive at the 5-HT1A receptor. The fact that 1-methylpsilocin displays greater pharmacological selectivity than psilocin indicates that 1-methylpsilocin represents a potentially useful alternative to psilocybin for development as a potential therapeutic agent.

scholarly journals Inhibitory deficits in euthymic bipolar disorder patients assessed in the human behavioral pattern monitor

2013 ◽  
Vol 150 (3) ◽  
pp. 948-954 ◽  
Author(s):  
Brook L. Henry ◽  
Arpi Minassian ◽  
Virginie M. Patt ◽  
Jessica Hua ◽  
Jared W. Young ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Behavioral Pattern ◽  
Inhibitory Deficits ◽  
Behavioral Pattern Monitor

scholarly journals A reverse-translational approach to bipolar disorder: Rodent and human studies in the Behavioral Pattern Monitor

2007 ◽  
Vol 31 (6) ◽  
pp. 882-896 ◽  
Author(s):  
Jared W. Young ◽  
Arpi Minassian ◽  
Martin P. Paulus ◽  
Mark A. Geyer ◽  
William Perry
Keyword(s):  
Bipolar Disorder ◽  
Behavioral Pattern ◽  
Human Studies ◽  
Behavioral Pattern Monitor ◽  
Translational Approach

Positron Emission Tomography of Cocaine Binding Sites on the Dopamine Transporter

1994 ◽  
Author(s):  
Bertha K. Madras ◽  
◽  
David R. Elmaleh ◽  
Peter C. Meltzer ◽  
Anna Y. Liung ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Dopamine Transporter ◽  
Binding Sites ◽  
Emission Tomography ◽  
Positron Emission
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