BEHAVIORAL AND NEUROCHEMICAL DYSFUNCTION IN THE CIRCLING (CI) RAT - ANOVEL GENETIC ANIMAL-MODEL OF A MOVEMENT DISORDER

One of the crucial breakthroughs in research on parkinsonism was the o bservation of circling behaviour in rodents after unilateral intranigr al injection of 6-hydroxydopamine. This Ungerstedt model remains one o f the basic animal models of Parkinson's disease. We report here the f irst mutant rat strain with abnormal circling behaviour and several ot her features reminiscent of the Ungerstedt Parkinson model. The neurol ogical disorder in the novel mutant rat strain is determined monogenet ically by a recessive autosomal gene termed circling (ci). Mutant rats of both genders exhibit an intense asymmetric circling in an open-fie ld or rotometer, which is enhanced by treatment with amphetamine. Neur ochemical determinations show that mutants of both genders have signif icantly lower concentrations of dopamine and dopamine metabolites in t he striatum ipsilateral to the preferred direction of rotation. Furthe rmore, in a forelimb-reaching test for assessing the skilled motor cap acities of rats, ci rats show a marked deficit on the side contralater al to the preferred direction of turning, which is analogous to motor deficits previously described for rats subjected to unilateral 6-hydro xydopamine lesions. The new mutant rat strain thus exhibits remarkable similarities to the Ungerstedt model and could be used to study the e ndogenous processes, particularly the genetic components, that might e ventually lead to progressive motor dysfunctions. Copyright (C) 1996 I BRO. Published by Elsevier Science Ltd.