title: Genetic and Modeling Approaches Reveal Distinct Components of Impulsive Behavior.
abstract: Impulsivity is an endophenotype found in many psychiatric disorders including substance use disorders, pathological gambling, and attention deficit hyperactivity disorder. Two behavioral features often considered in impulsive behavior are behavioral inhibition (impulsive action) and delayed gratification (impulsive choice). However, the extent to which these behavioral constructs represent distinct facets of behavior with discrete biological bases is unclear. To test the hypothesis that impulsive action and impulsive choice represent statistically independent behavioral constructs in mice, we collected behavioral measures of impulsivity in a single cohort of mice using well-validated operant behavioral paradigms. Mice with manipulation of serotonin 1B receptor (5-HT1BR) expression were included as a model of disordered impulsivity. A factor analysis was used to characterize correlations between the measures of impulsivity and to identify covariates. Using two approaches, we dissociated impulsive action from impulsive choice. First, the absence of 5-HT1BRs caused increased impulsive action, but not impulsive choice. Second, based on an exploratory factor analysis, a two-factor model described the data well, with measures of impulsive action and choice separating into two independent factors. A multiple-indicator multiple-causes analysis showed that 5-HT1BR expression and sex were significant covariates of impulsivity. Males displayed increased impulsivity in both dimensions, whereas 5-HT1BR expression was a predictor of increased impulsive action only. These data support the conclusion that impulsive action and impulsive choice are distinct behavioral phenotypes with dissociable biological influences that can be modeled in mice. Our work may help inform better classification, diagnosis, and treatment of psychiatric disorders, which present with disordered impulsivity.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Nautiyal
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.|Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Wall
authors.affiliation: Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Magalong
authors.affiliation: Department of Psychiatry, Translational Neuroscience Program; Center for Neuroscience Program and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ahmari
authors.affiliation: Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.|Psychology Departments, Barnard College and Columbia University, New York, NY, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Balsam
authors.affiliation: Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Blanco
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.|Department of Pharmacology, Columbia University, New York, NY, USA.
authors.forename: René
authors.initials: R
authors.lastname: Hen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D065786:Delay Discounting / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007175:Impulsive Behavior / Q000502:physiology*; D007266:Inhibition, Psychological; D008297:Male; D008822:Mice, Transgenic; D044302:Receptor, Serotonin, 5-HT1B / Q000172:deficiency / Q000502:physiology*; D012737:Sex Factors
chemical_list: D044302:Receptor, Serotonin, 5-HT1B