WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine
Abstract
Cocaine-induced synaptic plasticity in the nucleus accumbens is implicated in neural adaptations that underlie addiction. Here we demonstrate that Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein 1 (WAVE1) plays a selective role in medium spiny projection neurons that express D1 dopamine receptors (D1-MSNs) in the cellular and behavioral actions of cocaine. Our results suggest that chronic exposure to cocaine, followed by withdrawal, potentiates the signaling capacity of D1 dopamine and NMDA glutamate receptors, allowing WAVE1 activation in response to an acute cocaine challenge. WAVE1 activation is associated with morphological and functional decreases in glutamatergic synapses on D1-MSNs. Thus, we propose that WAVE1 is involved in a negative feedback mechanism of regulation of glutamatergic synapses as a part of the process of cocaine-induced synaptic plasticity.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 23, 2017
- Source ID
- 10.1073/pnas.1621185114
Entities
People
- Angus C. Nairn
- Dalton J. Surmeier
- David Dietz
- Eric J. Nestler
- Ilaria Ceglia
- Ko-woon Lee
- Michael E. Cahill
- Paul Greengard
- Steven M. Graves
- Yong Kim
Organizations
- Icahn School of Medicine at Mount Sinai
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- National Institute on Drug Abuse
- Northwestern University
- The Rockefeller University
- United States Department of Defense
- University at Buffalo
- Yale University