Behavioral and Structural Responses to Chronic Cocaine Require a Feedforward Loop Involving ΔFosB and Calcium/Calmodulin-Dependent Protein Kinase II in the Nucleus Accumbens Shell

• DOI: 10.1523/jneurosci.5192-12.2013
• Publication Date: 2013-03-06T17:55:06Z
• Authors: Alfred J. Robison; Vincent Vialou; Michelle Mazei-Ro...; Jian Feng; Saïd Kourrich; Miles Collins; Sunmee Wee; George Koob; Gustavo Turecki; Rachael Neve; Mark Thomas; Eric J. Nestler
• Keywords: FOSB; Medium spiny neuron; CAMK

The transcription factor ΔFosB and the brain-enriched calcium/calmodulin-dependent protein kinase II (CaMKIIα) are induced in nucleus accumbens (NAc) by chronic exposure to cocaine or other psychostimulant drugs of abuse, which two proteins mediate sensitized drug responses. Although CaMKIIα both regulate AMPA glutamate receptor expression function NAc, dendritic spine formation on NAc medium spiny neurons (MSNs), locomotor sensitization cocaine, no direct link between these molecules has date been explored. Here, we demonstrate that is phosphorylated at protein-stabilizing Ser27 CaMKII required for cocaine-mediated accumulation rat NAc. Conversely, show necessary sufficient induction gene vivo , an effect selective D 1 -type MSNs shell subregion. Furthermore, spines increased behavioral responsiveness after overexpression dependent. Importantly, first time human addicts, suggesting possible targets future therapeutic intervention. These data establish engage a cell-type- brain-region-specific positive feedforward loop as key mechanism regulating reward circuitry brain response cocaine.