D2 receptor stimulation, but not D1, restores striatal equilibrium in a rat model of Parkinsonism.
In Parkinson's disease dopamine depletion imbalances the two major output pathways of the striatum. L-DOPA replacement therapy is believed to correct this imbalance by providing effective D1 and D2 receptor stimulation to striatonigral and striatopallidal neurons, respectively. Here we tested this assumption in the rat model of Parkinsonism by monitoring the spike response of identified striatal neurons to cortical stimulation. As predicted, in 6-hydroxydopamine lesioned rats we observed that L-DOPA (6 mg/kg+benserazide), apomorphine and the D2 agonist quinpirole (0.5 mg/kg i.p.) counteract the enhanced responsiveness of striatopallidal neurons. Unexpectedly, the depressed responsiveness of striatonigral neurons was corrected by quinpirole whereas D1 stimulation exerted no (apomorphine, cPB) or worsening effects (L-DOPA, SKF38393 10 mg/kg). Therefore, quinpirole, but not D1 stimulation, restores functional equilibrium between the two striatal output pathways. Our results might explain the therapeutic effect of D2-based medications in Parkinson's disease.
Ballion
Bérangère
B
University of Bordeaux, Bordeaux, CNRS UMR 5227, Bordeaux F-33076, France.
Frenois
Francois
F
Zold
Camila L
CL
Chetrit
Jonathan
J
Murer
M Gustavo
MG
Gonon
Francois
F
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D001545:Benserazide / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001545:Benserazide; D016627:Oxidopamine; D001058:Apomorphine