Differential effects of a small, unilateral, 6-hydroxydopamine-induced nigral lesion on behavior in high and low responders to novelty.
The goal of this study was to develop an animal model that evaluates striatal-specific behavior after partial, unilateral destruction of nigrostriatal neurons. 6-OHDA (1 microg) was injected intranigrally (day 0) to reduce dopaminergic innervation of the dorsal striatum (DS); 6-OHDA (5 microg) was injected to reduce innervation of DS and nucleus accumbens (ACC). We analyzed changes in (a) behavior regulated by dopamine (DA) release in the DS (hindpaw preference from day 5 to day 19, every other day) and the ACC (novelty-induced locomotion on day 16) and (b) apomorphine-induced rotation (on day 21). We used two types of rat that show differences in structure and function of the dopaminergic neurons, namely high (HR) and low (LR) responders to novelty. 6-OHDA (1 microg) significantly decreased TH immunoreactivity (TH-ir) in the DS and increased preference for the hindpaw controlled by the nonlesioned side in HRs and LRs in time. Only in LRs was the significant increase of novelty-induced locomotion accompanied by a significant increase in TH-ir density in the ACC: this suggests a lesion-induced shift in nigrostriatal/mesolimbic balance toward a dominance of the mesolimbic system. The higher 6-OHDA dose significantly decreased TH-ir in the DS and the ACC and increased preference for the hindpaw controlled by the nonlesioned side in HRs and LRs in time. However, this increase occurred significantly earlier in LRs than in HRs. Apomorphine elicited contralateral rotations solely in LRs, and not in HRs, indicating development of supersensitive dopamine receptors in the DS of LRs, but not HRs. The data show that LRs are more susceptible to 6-OHDA than HRs. The relevance of the present data for Parkinson's disease is discussed.
van Oosten
R V
RV
Department of Psychoneuropharmacology, University of Nijmegen, Nijmegen, The Netherlands.
Cools
A R
AR
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000008:administration & dosage; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine