Hemiparkinsonian rats rotate toward the side with the weaker dopaminergic neurotransmission.
Rats with unilateral lesion of the substantia nigra pars compacta (SNpc) have been used as a model of Parkinson's disease. Depending on the lesion protocol and on the drug challenge, these rats rotate in opposite directions. The aim of the present study was to propose a model to explain how critical factors determine the direction of these turns. Unilateral lesion of the SNpc was induced with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Separate analysis showed that neither the type of neurotoxin nor the site of lesion along the nigrostriatal pathway was able to predict the direction of the turns these rats made after they were challenged with apomorphine. However, the combination of these two factors determined the magnitude of the lesion estimated by tyrosine-hydroxylase immunohistochemistry and HPLC-ED measurement of striatal dopamine. Very small lesions did not cause turns, medium-size lesions caused ipsiversive turns, and large lesions caused contraversive turns. Large-size SNpc lesions resulted in an increased binding of [(3)H]raclopride to D2 receptors, while medium-size lesions reduced the binding of [(3)H]SCH-23390 D1 receptors in the ipsilateral striatum. These results are coherent with the model proposing that after challenged with a dopamine receptor agonist, unilaterally SNpc-lesioned rats rotate toward the side with the weaker activation of dopamine receptors. This activation is weaker on the lesioned side in animals with small SNpc lesions due to the loss of dopamine, but stronger in animals with large lesions due to dopamine receptor supersensitivity.
Da Cunha
Claudio
C
Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, UFPR, Curitiba, PR, Brazil. dacunha@ufpr.br
Wietzikoski
Evellyn Claudia
EC
Ferro
Marcelo Machado
MM
Martinez
Glaucia Regina
GR
Vital
Maria Aparecida Barbato Frazão
MA
Hipólide
Débora
D
Tufik
Sergio
S
Canteras
Newton Sabino
NS
D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001925:Brain Damage, Chronic / Q000139:chemically induced; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D020267:MPTP Poisoning / Q000378:metabolism / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology
D018491:Dopamine Agonists; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine