Stressful events rapidly trigger activity-dependent synaptic plasticity in certain brain areas, d... more Stressful events rapidly trigger activity-dependent synaptic plasticity in certain brain areas, driving the formation of aversive memories. However, it remains unclear how stressful experience affects plasticity mechanisms to regulate learning of appetitive events, such as intake of addictive drugs or palatable foods. Using rats, we show that two acute stress mediators, corticotropin-releasing factor (CRF) and norepinephrine (NE), enhance plasticity of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA) through their differential effects on inositol 1,4,5-triphosphate (IP 3 )-dependent Ca 2+ signaling. In line with this, acute social defeat stress engages convergent CRF and NE signaling in the VTA to enhance learning of cocaine-paired cues. Furthermore, defeat stress enables learning of a food-paired cue with no delay between the cue onset and food delivery. We propose that acute stress mediators synergistically regulate IP 3 -Ca 2+ signaling in the...
Graphical Abstract Highlights d CRF and a1ARs converge on IP 3-Ca 2+ signaling to enhance NMDA pl... more Graphical Abstract Highlights d CRF and a1ARs converge on IP 3-Ca 2+ signaling to enhance NMDA plasticity d Acute social defeat stress promotes cocaine place conditioning d CRF and a1ARs work in concert in the VTA to enhance cocaine conditioning
Stressful events rapidly trigger activity-dependent synaptic plasticity in certain brain areas, d... more Stressful events rapidly trigger activity-dependent synaptic plasticity in certain brain areas, driving the formation of aversive memories. However, it remains unclear how stressful experience affects plasticity mechanisms to regulate learning of appetitive events, such as intake of addictive drugs or palatable foods. Using rats, we show that two acute stress mediators, corticotropin-releasing factor (CRF) and norepinephrine (NE), enhance plasticity of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA) through their differential effects on inositol 1,4,5-triphosphate (IP 3 )-dependent Ca 2+ signaling. In line with this, acute social defeat stress engages convergent CRF and NE signaling in the VTA to enhance learning of cocaine-paired cues. Furthermore, defeat stress enables learning of a food-paired cue with no delay between the cue onset and food delivery. We propose that acute stress mediators synergistically regulate IP 3 -Ca 2+ signaling in the...
Graphical Abstract Highlights d CRF and a1ARs converge on IP 3-Ca 2+ signaling to enhance NMDA pl... more Graphical Abstract Highlights d CRF and a1ARs converge on IP 3-Ca 2+ signaling to enhance NMDA plasticity d Acute social defeat stress promotes cocaine place conditioning d CRF and a1ARs work in concert in the VTA to enhance cocaine conditioning
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Papers by Russell Kan