Effects of long-term treatment with dopamine receptor agonists and antagonists on terminal arbor size

• Published in: The European journal of neuroscience 2002-09, Vol.16 (5), p.787-794
• Main Authors: Parish, C. L., Stanic, D., Drago, J., Borrelli, E., Finkelstein, D. I., Horne, M. K.
• Format: Article
• Language: English
• Subjects: Animals; Axons - drug effects; Cocaine - adverse effects; Dopamine; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Dopamine D2 Receptor Antagonists; Dopamine Plasma Membrane Transport Proteins; Immunohistochemistry; Life Sciences; Male; Membrane Glycoproteins; Membrane Transport Proteins - analysis; Mice; Mice, Knockout; Nerve Tissue Proteins; Neurons and Cognition; Parkinson's disease; plasticity; Rats; Rats, Wistar; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - genetics; sprouting; Substantia Nigra - anatomy & histology; Substantia Nigra - cytology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.2002.02132.x

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.