CaMKII Modulates Diacylglycerol Lipase-α Activity in the Rat Nucleus Accumbens after Incubation of Cocaine Craving

• DOI: 10.1523/eneuro.0220-21.2021
• Publication Date: 2021-09-20T17:53:12Z
• Authors: Conor H. Murray; Andrew D. Gaulden; Alex B. Kawa; Mike Milovanovic; Aaron J. Caccamise; Jonathan R. Funke; Sachin Patel; Marina E. Wolf
• Keywords: Rats, Sprague-Dawley; 0301 basic medicine; Lipoprotein Lipase; 03 medical and health sciences; Cocaine; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Research Article: New Research; Nucleus Accumbens; Craving; Rats; Substance Withdrawal Syndrome

Abstract Relapse is a major challenge to the treatment of substance use disorders. A progressive increase in cue-induced drug craving, termed incubation observed after withdrawal from multiple drugs abuse humans and rodents. Incubation cocaine craving involves strengthening excitatory synapses onto nucleus accumbens (NAc) medium spiny neurons via postsynaptic accumulation high-conductance Ca 2+ -permeable AMPA receptors. This enhances reactivity drug-associated cues required for expression incubation. Additionally, associated with loss synaptic depression normally triggered by stimulation metabotropic glutamate receptor 5 (mGlu5), leading endocannabinoid production, expressed presynaptically cannabinoid 1 activation. Previous studies have found alterations mGlu5 Homer proteins this depression. Here we conducted coimmunoprecipitation investigate associations diacylglycerol lipase-α (DGL), which catalyzes formation 2-arachidonylglycerol (2-AG), proteins. Although these interactions were unchanged NAc core at incubation-relevant times, association DGL total phosphorylated /calmodulin-dependent protein kinase IIα (CaMKIIα) CaMKIIβ was increased. would be predicted, based on other studies, inhibit activity therefore 2-AG production. confirmed measuring enzymatic activity. However, magnitude inhibition did not correlate individual rats. These results suggest that CaMKII contributes mGlu5-dependent incubation, but functional significance remains unclear.