Effects of long-term treatment with dopamine receptor agonists and antagonists on terminal arbor size.
This study demonstrates that pharmacological manipulation of the dopamine (DA) receptors can modulate the size of the axonal tree of substantia nigra pars compacta (SNpc) neurons in mice. Pharmacological blockade or genetic ablation of the D2 receptor (D2R) resulted in sprouting of DA SNpc neurons whereas treatment with a D2 agonist resulted in pruning of the terminal arbor of these neurons. Agents such as cocaine, that indirectly stimulate D2R, also resulted in reduced terminal arbor. Specific D1 agonists or antagonists had no effect on the density of DA terminals in the striatum. We conclude that the D2 receptor has a central role in regulating the size of the terminal arbor of nigrostriatal neurons. These findings have implications relating to the use of dopaminergic agonists in the management of Parkinson's disease and in controlling plasticity following injury, loss or transplantation of DA neurons.
Parish
C L
CL
Neurosciences Group, Department of Medicine, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton 3168, Australia.
Stanic
D
D
Drago
J
J
Borrelli
E
E
Finkelstein
D I
DI
Horne
M K
MK
D000818:Animals; D001369:Axons / Q000187:drug effects*; D003042:Cocaine / Q000009:adverse effects; D004298:Dopamine; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000235:genetics; D013378:Substantia Nigra / Q000033:anatomy & histology* / Q000166:cytology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine; D004298:Dopamine