Behavioral and neurochemical dysfunction in the circling (ci) rat: a novel genetic animal model of a movement disorder.
One of the crucial breakthroughs in research on parkinsonism was the observation of circling behaviour in rodents after unilateral intranigral injection of 6-hydroxydopamine. This Ungerstedt model remains one of the basic animal models of Parkinson's disease. We report here the first mutant rat strain with abnormal circling behaviour and several other features reminiscent of the Ungerstedt Parkinson model. The neurological disorder in the novel mutant rat strain is determined monogenetically by a recessive autosomal gene termed circling (ci). Mutant rats of both genders exhibit an intense asymmetric circling in an open-field or rotometer, which is enhanced by treatment with amphetamine. Neurochemical determinations show that mutants of both genders have significantly lower concentrations of dopamine and dopamine metabolites in the striatum ipsilateral to the preferred direction of rotation. Furthermore, in a forelimb-reaching test for assessing the skilled motor capacities of rats, ci rats show a marked deficit on the side contralateral to the preferred direction of turning, which is analogous to motor deficits previously described for rats subjected to unilateral 6-hydroxydopamine lesions. The new mutant rat strain thus exhibits remarkable similarities to the Ungerstedt model and could be used to study the endogenous processes, particularly the genetic components, that might eventually lead to progressive motor dysfunctions.
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
W
W
Löscher
A
A
Richter
G
G
Nikkhah
C
C
Rosenthal
U
U
Ebert
H J
HJ
Hedrich
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005552:Forelimb / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009069:Movement Disorders / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D009154:Mutation; D051381:Rats; D011917:Rats, Inbred Lew; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D000978:Antiparkinson Agents; D000697:Central Nervous System Stimulants; D018690:Excitatory Amino Acid Agonists; D016291:Dizocilpine Maleate; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine