Abnormal circling behavior in rat mutants and its relevance to model specific brain dysfunctions

Circling or rotational behavior is the most studied indicator of cerebral asymmetry in the rat. In humans, disturbances in cerebral asymmetry are involved in the etiology of several psychiatric disorders, including schizophrenia, Tourette syndrome and attention-deficit hyperactivity disorder. Abnormal rotational behavior in rodents is indicative of either an imbalance of forebrain dopamine systems, particularly an imbalance of nigrostriatal function, or an inner ear disease affecting the vestibular (balance) system. Abnormally enhanced circling behavior has been described in several mutant rat and mouse strains both with and without defects of the vestibular system. However, the relationship between vestibular defects and lateralized circling in rodents is only incompletely understood. In this review, we describe and discuss various spontaneous mutations associated with abnormal circling behavior in different rat strains and their potential relevance to model specific brain dysfunctions. The circling rat mutants described in this review illustrate how genetic animal models may serve to study multifaceted brain functions and dysfunctions, including disorders of the basal ganglia and vestibular system.