Pharmacological analysis of extracellular dopamine and metabolites in the striatum of conscious as/agu rats, mutants with locomotor disorder.
The as/agu rat is a spontaneously occurring mutation which exhibits locomotor abnormalities, reduced tyrosine hydroxylase levels in the substantia nigra and lower extracellular levels of dopamine. The animal could represent a model of some human locomotor disorders. High-potassium medium evoked a 460% rise of dopamine levels in control rats but double this in mutants. Amphetamine increased extracellular dopamine by 710% in controls and 1480% in mutants. Clorgyline produced a small increase of dopamine levels in controls but an 1170% increase in mutants. The uptake inhibitor nomifensine increased dopamine levels by 910% in controls but only 270% in mutants. After treatment with benserazide plus L-DOPA, an acute injection of L-DOPA evoked a release of dopamine which was twice as large in the as/agu rats compared with controls. The results show reduced extracellular dopamine in as/agu rats when the locomotor disorder is apparent, but there has been little loss of tyrosine hydroxylase. The responses to drugs are qualitatively different from those obtained using 6-hydroxydopamine.Overall, the effects of compounds affecting aminergic neurons suggest that one possible mechanism for the neuronal abnormality in as/agu rats is a defective regulation of dopamine release from striatal terminals.
Campbell
J M
JM
Institute of Biomedical and Life Sciences, University of Glasgow, G12 8QQ, Glasgow, UK.
Gilmore
D P
DP
Russell
D
D
Growney
C A
CA
Favor
G
G
Kennedy
A K
AK
Davies
R W
RW
Payne
A P
AP
Stone
T W
TW
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009069:Movement Disorders / Q000235:genetics* / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012016:Reference Values
D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D008996:Monoamine Oxidase Inhibitors; D009627:Nomifensine; D007980:Levodopa; D000661:Amphetamine; D003010:Clorgyline; D011188:Potassium; D004298:Dopamine