Dopamine-receptor stimulation: biobehavioral and biochemical consequences.
The MPTP monkey is a well-characterized animal model of parkinsonism and provides an exceptional tool for the study of dyskinesias induced by dopamine-like agents. Several such agents have been tested during the past 15 years, and it has been found that the duration of action of these compounds is the most reliable variable with which to predict their dyskinesiogenic profile. It is proposed that L-dopa-induced dyskinesias represent a form of pathological learning caused by chronic pulsatile (nonphysiological) stimulation of dopamine receptors, which activates a cascade of molecular and biochemical events. These events include defective regulation of Fos proteins that belong to the deltaFosB family, increased expression of neuropeptides, and defective GABA- and glutamate-mediated neurotransmission in the output structures of the basal ganglia.
Calon
F
F
Oncology and Molecular Endocrinology Research Unit, Laval University Medical Center CHUL, Québec, Canada.
Hadj Tahar
A
A
Blanchet
P J
PJ
Morissette
M
M
Grondin
R
R
Goulet
M
M
Doucet
J P
JP
Robertson
G S
GS
Nestler
E
E
Di Paolo
T
T
Bédard
P J
PJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D000882:Haplorhini; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects*; D009433:Neural Inhibition; D009479:Neuropeptides / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine