title: Appetitive cue-evoked ERK signaling in the nucleus accumbens requires NMDA and D1 dopamine receptor activation and regulates CREB phosphorylation.
abstract: Conditioned stimuli (CS) can modulate reward-seeking behavior. This modulatory effect can be maladaptive and has been implicated in excessive reward seeking and relapse to drug addiction. We previously demonstrated that exposure to an appetitive CS causes an increase in the activation of extracellular signal-regulated kinase (ERK) and cyclic-AMP response-element binding protein (CREB) in the nucleus accumbens (NAc) of rats, and that CS-evoked ERK activation is critical for CS control over reward seeking. To elucidate the mechanism that mediates CS-driven ERK activation in the NAc, we selectively blocked NMDA glutamate or D1 dopamine receptors in the NAc. To determine whether CS-driven ERK and CREB activation are linked, we selectively blocked ERK signaling in the NAc. We found that both NMDA and D1 receptors are critical for CS-driven ERK signaling in the NAc, and that this recruitment of the ERK cascade is responsible for increased CREB activation in the presence of the CS. Our findings suggest that activation of the NMDAR-D1R/ERK/CREB signal transduction pathway plays a critical role in the control of reward-seeking behavior by reward-predictive cues.
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Erin K Z
authors.initials: EK
authors.lastname: Kirschmann
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Jocelyn C
authors.initials: JC
authors.lastname: Mauna
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Willis
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Foster
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Chipman
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA thiels@pitt.edu.
authors.forename: Edda
authors.initials: E
authors.lastname: Thiels
mesh_terms: D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D003463:Cues; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012201:Reward
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate