TY - JOUR
T1 - Loss of dysbindin-1 in mice impairs reward-based operant learning by increasing impulsive and compulsive behavior
AU - Carr, Gregory V.
AU - Jenkins, Kimberly A.
AU - Weinberger, Daniel R.
AU - Papaleo, Francesco
N1 - Funding Information:
We thank Qingjun Tian and Jingshan Chen for technical assistance and Audrey Bebensee, Randy Xun, and Omoye Akhile for critical review of the manuscript. This research was supported by the National Institute of Mental Health Intramural Research Program , by the NIMH Julius Axelrod Memorial Fellowship Training Award , and by the Marie Curie FP7 Reintegration Grant No. 268247 . The authors declare that they have no financial conflicts of interest.
PY - 2013/3/5
Y1 - 2013/3/5
N2 - The dystrobrevin-binding protein 1 (DTNBP1) gene, which encodes the dysbindin-1 protein, is a potential schizophrenia susceptibility gene. Polymorphisms in the DTNBP1 gene have been associated with altered cognitive abilities. In the present study, dysbindin-1 null mutant (dys-/-), heterozygous (dys+/-), and wild-type (dys+/+) mice, on a C57BL/6J genetic background, were tested in either a match to sample or nonmatch to sample visual discrimination task. This visual discrimination task was designed to measure rule learning and detect any changes in response timing over the course of testing. Dys-/- mice displayed significant learning deficits and required more trials to acquire this task. However, once criterion was reached, there were no differences between the genotypes on any behavioral measures. Dys-/- mice exhibited increased compulsive and impulsive behaviors compared to control littermates suggesting the inability to suppress incorrectly-timed responses underlies their increased time to acquisition. Indeed, group comparisons of behavior differences between the first and last day of testing showed that only dys-/- mice consistently decreased measures of perseverative, premature, timeout, and total responses. These findings illustrate how some aspects of altered cognitive performance in dys-/- mice might be related to increased impulsive and compulsive behaviors, analogous to cognitive deficits in some individuals with psychiatric disorders.
AB - The dystrobrevin-binding protein 1 (DTNBP1) gene, which encodes the dysbindin-1 protein, is a potential schizophrenia susceptibility gene. Polymorphisms in the DTNBP1 gene have been associated with altered cognitive abilities. In the present study, dysbindin-1 null mutant (dys-/-), heterozygous (dys+/-), and wild-type (dys+/+) mice, on a C57BL/6J genetic background, were tested in either a match to sample or nonmatch to sample visual discrimination task. This visual discrimination task was designed to measure rule learning and detect any changes in response timing over the course of testing. Dys-/- mice displayed significant learning deficits and required more trials to acquire this task. However, once criterion was reached, there were no differences between the genotypes on any behavioral measures. Dys-/- mice exhibited increased compulsive and impulsive behaviors compared to control littermates suggesting the inability to suppress incorrectly-timed responses underlies their increased time to acquisition. Indeed, group comparisons of behavior differences between the first and last day of testing showed that only dys-/- mice consistently decreased measures of perseverative, premature, timeout, and total responses. These findings illustrate how some aspects of altered cognitive performance in dys-/- mice might be related to increased impulsive and compulsive behaviors, analogous to cognitive deficits in some individuals with psychiatric disorders.
KW - Compulsivity
KW - Dysbindin
KW - Impulsivity
KW - Operant learning
KW - Schizophrenia
KW - Timing
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U2 - 10.1016/j.bbr.2012.12.021
DO - 10.1016/j.bbr.2012.12.021
M3 - Article
C2 - 23261874
AN - SCOPUS:84872038495
SN - 0166-4328
VL - 241
SP - 173
EP - 184
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -