Is there an inhibitory-response-control system in the rat? Evidence from anatomical and pharmacological studies of behavioral inhibition

Many common psychiatric conditions, such as attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), Parkinson's disease, addiction and pathological gambling are linked by a failure in the mechanisms that control, or inhibit, inappropriate behavior. Models of rat behavioral inhibition permit us to study in detail the anatomical and pharmacological bases of inhibitory failure, using methods that translate directly with patient assessment in the clinic. This review updates current ideas relating to behavioral inhibition based on two significant lines of evidence from rat studies: (1) To integrate new findings from the stop-signal task into existing models of behavioral inhibition, in particular relating to 'impulsive action' control. The stop-signal task has been used for a number of years to evaluate psychiatric conditions and has recently been translated for use in the rat, bringing a wealth of new information to behavioral inhibition research. (2) To consider the importance of the subthalamic nucleus (STN) in the neural circuitry of behavioral inhibition. This function of this nucleus is central to a number of 'disinhibitory' disorders such as Parkinson's disease and OCD, and their therapies, but its role in behavioral inhibition is still undervalued, and often not considered in preclinical models of behavioral control. Integration of these findings has pinpointed the orbitofrontal cortex (OF), dorsomedial striatum (DMStr) and STN within a network that normally inhibits many forms of behavior, including both impulsive and compulsive forms. However, there are distinct differences between behavioral subtypes in their neurochemical modulation. This review brings new light to the classical view of the mechanisms that inhibit behavior, in particular suggesting a far more prominent role for the STN, a structure that is usually omitted from conventional behavioral-inhibition networks. The OF-DMStr-STN circuitry may form the basis of a control network that defines behavioral inhibition and that acts to suppress or countermand many forms of inappropriate or maladaptive behavior. (C) 2009 Elsevier Ltd. All rights reserved.