Enhancement of dopamine-induced signaling responses in the forebrain of mice lacking dopamine D3 receptor.
It is well known that the dopamine D(3) receptor plays a critical role in several psychological disorders, such as drug dependence. The present study was designed to investigate the influence of lacking dopamine D(3) receptors in dopamine-induced G-protein activation and Ca(2+) influx in the mouse forebrain. The deletion of dopamine D(3) receptor gene caused the enhancement of dopamine-induced G-protein activation in the limbic forebrain of dopamine D(3) receptor knockout (D(3)KO) mice. Furthermore, the dopamine-induced Ca(2+) influx was enhanced in the coculture of neuron/glia cells obtained from the forebrain of D(3)KO mice. The present data provide direct evidence that a deletion of central dopamine D(3) receptor enhances the dopamine D(1)/D(2) receptor-mediated intracellular signaling.
Mizuo
Keisuke
K
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Narita
Minoru
M
Miyatake
Mayumi
M
Suzuki
Tsutomu
T
D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000235:genetics; D050637:Receptors, Dopamine D3; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
C493594:Drd3 protein, mouse; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004298:Dopamine