Rats Lacking the Dopamine Transporter Display Inflexibility in Innate and Learned Behavior.

Abstract

Playing a key role in the organization of striatal motor output, the dopamine (DA)-ergic system regulates both innate and complex learned behaviors. Growing evidence clearly indicates the involvement of the DA-ergic system in different forms of repetitive (perseverative) behavior. Some of these behaviors accompany such disorders as obsessive-compulsive disorder (OCD), Tourette's syndrome, schizophrenia, and addiction. In this study, we have traced how the inflexibility of repetitive reactions in the recently developed animal model of hyper-DA-ergia, dopamine transporter knockout rats (DAT-KO rats), affects the realization of innate behavior (grooming) and the learning of spatial (learning and reversal learning in T-maze) and non-spatial (extinction of operant reaction) tasks. We found that the microstructure of grooming in DAT-KO rats significantly differed in comparison to control rats. DAT-KO rats more often demonstrated a fixed syntactic chain, making fewer errors and very rarely missing the chain steps in comparison to control rats. DAT-KO rats' behavior during inter-grooming intervals was completely different to the control animals. During learning and reversal learning in the T-maze, DAT-KO rats displayed pronounced patterns of hyperactivity and perseverative (stereotypical) activity, which led to worse learning and a worse performance of the task. Most of the DAT-KO rats could not properly learn the behavioral task in question. During re-learning, DAT-KO rats demonstrated rigid perseverative activity even in the absence of any reinforcement. In operant tasks, the mutant rats demonstrated poor extinction of operant lever pressing: they continued to perform lever presses despite no there being reinforcement. Our results suggest that abnormally elevated DA levels may be responsible for behavioral rigidity. It is conceivable that this phenomenon in DAT-KO rats reflects some of the behavioral traits observed in clinical conditions associated with endogenous or exogenous hyper-DA-ergia, such as schizophrenia, substance abuse, OCD, patients with Parkinson disease treated with DA mimetics, etc. Thus, DAT-KO rats may be a valuable behavioral model in the search for new pharmacological approaches to treat such illnesses.