| Autor: |
Estrada-Sánchez AM; Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.; División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica (IPICYT), Camino a la Presa San José No. 2055, Colonia Lomas 4a Sección, San Luis Potosi C.P. 78216, Mexico., Rangel-Barajas C; Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA., Howe AG; Psychology Department, University of California Los Angeles, Los Angeles, CA 90095, USA.; Intelligent Systems Laboratory, HRL Laboratories, LLC., Malibu, CA 90265, USA., Barton SJ; Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA., Mach RH; Department of Radiology, University of Pennsylvania School of Medicine, Chemistry Building, 231 S. 34th St., Philadelphia, PA 19104, USA., Luedtke RR; Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA., Rebec GV; Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA. |
| Abstrakt: |
D3 receptors, a key component of the dopamine system, have emerged as a potential target of therapies to improve motor symptoms across neurodegenerative and neuropsychiatric conditions. In the present work, we evaluated the effect of D3 receptor activation on the involuntary head twitches induced by 2,5-dimethoxy-4-iodoamphetamine (DOI) at behavioral and electrophysiological levels. Mice received an intraperitoneal injection of either a full D3 agonist, WC 44 [4-(2-fluoroethyl)-N-[4-[4-(2-methoxyphenyl)piperazin 1-yl]butyl]benzamide] or a partial D3 agonist, WW-III-55 [N-(4-(4-(4-methoxyphenyl)piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide] five minutes before the intraperitoneal administration of DOI. Compared to the control group, both D3 agonists delayed the onset of the DOI-induced head-twitch response and reduced the total number and frequency of the head twitches. Moreover, the simultaneous recording of neuronal activity in the motor cortex (M1) and dorsal striatum (DS) indicated that D3 activation led to slight changes in a single unit activity, mainly in DS, and increased its correlated firing in DS or between presumed cortical pyramidal neurons (CPNs) and striatal medium spiny neurons (MSNs). Our results confirm the role of D3 receptor activation in controlling DOI-induced involuntary movements and suggest that this effect involves, at least in part, an increase in correlated corticostriatal activity. A further understanding of the underlying mechanisms may provide a suitable target for treating neuropathologies in which involuntary movements occur. |
