Regional heterogeneity of D2-receptor signaling in the dorsal striatum and nucleus accumbens

• Autores: Marcott, Pamela F.; Gong, Sheng; Donthamsetti, Prashant; Grinnell, Steven G.; Nelson, Melissa N.; Newman, Amy H.; Birnbaumer, Lutz; Martemyanov, Kirill A.; Javitch, Jonathan A.; Ford, Christopher P.
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Neuron. 2018;98(3):575-587.e4
• Materia: DOPAMINA; ESQUIZOFRENIA; GANGLIOS; CEREBRO; ADICCION; COCAINA; NEUROTRANSMISORES
• Institución: Pontificia Universidad Católica Argentina

Fil: Marcott, Pamela F. University of Colorado. School of Medicine. Department of Pharmacology; Estados Unidos
Fil: Marcott, Pamela F. Case Western Reserve University. School of Medicine. Department of Physiology and Biophysics; Estados Unidos
Fil: Gong, Sheng. University of Colorado. School of Medicine. Department of Pharmacology; Estados Unidos
Fil: Gong, Sheng. Case Western Reserve University. School of Medicine. Department of Physiology and Biophysics; Estados Unidos
Fil: Donthamsetti, Prashant. Columbia University. Department of Pharmacology; Estados Unidos
Fil: Grinnell, Steven G. Columbia University. Department of Psychiatry; Estados Unidos
Fil: Grinnell, Steven G. New York State Psychiatric Institute. Division of Molecular Therapeutics; Estados Unidos
Fil: Nelson, Melissa N. Columbia University. Department of Psychiatry; Estados Unidos
Fil: New York State Psychiatric Institute. Division of Molecular Therapeutics; Estados Unidos
Fil: Nelson, Melissa N. National Institute of Drug Abuse. Intramural Research Program; Estados Unidos
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Martemyanov, Kirill A. The Scripps Research Institute. Department of Neuroscience; Estados Unidos
Fil: Javitch, Jonathan A. Columbia University. Department of Pharmacology; Estados Unidos
Fil: Javitch, Jonathan A. Columbia University. Department of Psychiatry; Estados Unidos
Fil: Javitch, Jonathan A. New York State Psychiatric Institute. Division of Molecular Therapeutics; Estados Unidos
Fil: Ford, Christopher P. University of Colorado. School of Medicine. Department of Pharmacology; Estados Unidos
Fil: Ford, Christopher P. Case Western Reserve University. School of Medicine. Department of Physiology and Biophysics; Estados Unidos
Abstract: Dopamine input to the dorsal and ventral striatum originates from separate populations of midbrain neurons. Despite differences in afferent inputs and behavioral output, little is known about how dopamine release is encoded by dopamine receptors on medium spiny neurons (MSNs) across striatal subregions. Here we examined the activation of D2 receptors following the synaptic release of dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) shell. We found that D2 receptor-mediated synaptic currents were slower in the NAc and this difference occurred at the level of D2-receptor signaling. As a result of preferential coupling to Gαo, we also found that D2 receptors in MSNs demonstrated higher sensitivity for dopamine in the NAc. The higher sensitivity in the NAc was eliminated following cocaine exposure. These results identify differences in the sensitivity and timing of D2-receptor signaling across the striatum that influence how nigrostriatal and mesolimbic signals are encoded across these circuits.