PMID- 14623353 OWN - NLM STAT- MEDLINE DCOM- 20040722 LR - 20190624 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 480 IP - 1-3 DP - 2003 Nov 7 TI - Brain-derived neurotrophic factor controls dopamine D3 receptor expression: therapeutic implications in Parkinson's disease. PG - 89-95 AB - Brain-derived neurotrophic factor (BDNF) belongs to a family of proteins related to nerve growth factor, which are responsible for neuron proliferation, survival and differentiation. A more diverse role for BDNF as a neuronal extracellular transmitter has, nevertheless, been proposed. Here we show that BDNF synthesized by dopamine neurons is responsible for the appearance of the dopamine D3 receptor during development and maintains its expression in adults. Moreover, BDNF triggers behavioral sensitization to levodopa in hemiparkinsonian rats. In monkeys rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which develop levodopa-induced dyskinesia, we show an overexpression of this receptor. Administration of a dopamine D3 receptor-selective partial agonist strongly attenuated levodopa-induced dyskinesia, while leaving unaffected the therapeutic effect of levodopa. These results suggest that the dopamine D3 receptor participates in both dyskinesia and the therapeutic action of levodopa and that partial agonists may normalize dopamine D3 receptor function and correct side-effects of levodopa therapy in PD patients. FAU - Guillin, Olivier AU - Guillin O AD - Unite de Neurobiologie et Pharmacologie Moleculaire, INSERM U 573, Centre Paul Broca, 2 ter rue d'Alesia, 75014, Paris, France. olivierguillin@yahoo.fr FAU - Griffon, Nathalie AU - Griffon N FAU - Bezard, Erwan AU - Bezard E FAU - Leriche, Ludovic AU - Leriche L FAU - Diaz, Jorge AU - Diaz J FAU - Gross, Christian AU - Gross C FAU - Sokoloff, Pierre AU - Sokoloff P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DRD3 protein, human) RN - 0 (Dopamine Agonists) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Dopamine D3) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*physiology/therapeutic use MH - Dopamine Agonists/pharmacology/therapeutic use MH - Gene Expression Regulation/drug effects MH - Humans MH - Parkinson Disease/*drug therapy/genetics/*metabolism MH - Protein Binding/drug effects/physiology MH - Receptors, Dopamine D2/agonists/*biosynthesis/genetics MH - Receptors, Dopamine D3 RF - 60 EDAT- 2003/11/19 05:00 MHDA- 2004/07/23 05:00 CRDT- 2003/11/19 05:00 PHST- 2003/11/19 05:00 [pubmed] PHST- 2004/07/23 05:00 [medline] PHST- 2003/11/19 05:00 [entrez] AID - S0014299903023914 [pii] AID - 10.1016/j.ejphar.2003.08.096 [doi] PST - ppublish SO - Eur J Pharmacol. 2003 Nov 7;480(1-3):89-95. doi: 10.1016/j.ejphar.2003.08.096.