Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats.
In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease, controversy exists concerning the use of apomorphine- or D-amphetamine-induced rotations as reliable indicators of nigrostriatal dopamine depletion. Our objective was to evaluate which, if either, drug-induced behavior is more predictive of the extent of nigrostriatal dopamine depletion. Fischer 344 and Sprague-Dawley rats were unilaterally injected with 9 micrograms/4 microliters/4 min 6-hydroxydopamine into the medial forebrain bundle. The animals were behaviorally tested with apomorphine (0.05 mg/kg, s.c.) and D-amphetamine (5.0 mg/kg, s.c.). Following testing, the brains were removed and the right and left striata, substantia nigra and ventral tegmental area were dissected free and quickly frozen at -70 degrees C for analysis of catecholamine content by high performance liquid chromatography coupled with electrochemical detection. Our results indicate that an animal which has greater than a 90% depletion of dopamine in the striatum might not rotate substantially on apomorphine, without a concomitant depletion of > 50% of the DA content in the corresponding substantia nigra. No correlations were seen involving depletions of the ventral tegmental area and the extent of the lesions to the striatum. Submaximally lesioned (75-90% depleted) rats were found to rotate on D-amphetamine but not on apomorphine. In addition, control rats that did not receive lesions were often seen to rotate extensively on D-amphetamine. We therefore conclude that maximal lesions of the striatum and substantia nigra are required to generate rotations demonstrable with low dose apomorphine but not with D-amphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Hudson
J L
JL
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
van Horne
C G
CG
Strömberg
I
I
Brock
S
S
Clayton
J
J
Masserano
J
J
Hoffer
B J
BJ
Gerhardt
G A
GA
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D016627:Oxidopamine; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine