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New Discoveries

NARC

N-Acetylcysteine Reduces Adolescent Marijuana Use (10/31/12)

Sculpting of the Extracellular Matrix is Necessary for Drug Cue-Induced Synaptic Plasticity & Relapse (November, 2014)

The extracellular matrix surrounds all cells in the brain, and is a protein-based matrix that signals to the cells in response to increased synaptic activity. Drug cues produce a very rapid potentiation in cortico-accumbens synapses that is required for the drug cue to induce relapse in the reinstatement animal model of relapse. Activation of matrix metalloproteases that control signaling in the extracellular matrix was found to be required for the transient synaptic potentiation mediating cued relapse to cocaine, heroin and nicotine. This striking finding opens the extracellular matrix and matrix metalloproteases as possible therapeutic targets for treating drug addiction.

Smith ACW, YM Kupchik, M.D. Scofield, CD Gipson and PW Kalivas. 2014. Synaptic plasticity mediating cocaine relapse requires matrix metalloproteinases. Nature Neuroscience, 17: 1655-1657, 2014. PMC4241163

Alex Smith led this research as part of his Ph.D. thesis in Neuroscience at MUSC, and is currently a postdoctoral fellow with Dr. Paul Kenny at Mt Sinai Medical College in NYC. Drs. Yoni Kupchik and Cassandra Gipson were postdoctoral fellows at MUSC, and now are Assistant Professors and the Hebrew University in Jerusalem or at Arizona State University, respectively. Dr. Mike Scofield is a current postdoctoral fellow in the lab.

D1-Expressing Accumbens Neurons Make Large Contributions to the Indirect Pathway by Making Functional Synapses in the Ventral Pallidum (July, 2015)

There is a great deal of emphasis in current basal ganglia neurobiology on the fact that striatal neurons express either D1 or D2 dopamine receptors, and that each cell type contributes to separate circuits and function. Thus, activation of D1 receptors is thought to selectively activate projection in the ‘direct’ pathway to the ventral mesencephalon and support behaviors that seek rewards, such as addictive drugs, while activation of D2 receptors activates striatal neurons projecting into the ‘indirect’ pathway to the pallidum and mediates inhibition of motivated behavior. A recent study by NARC investigators demonstrated that this distinction is not valid for projections from the nucleus accumbens, and may account for our previous observation that optogenetic inhibition of accumbens cells to the ventral pallidum prevented reinstated cocaine seeking, while inhibiting projections to the mesencephalon was ineffective. In conclusion, when it comes to understanding motivated behaviors, the regulation of behavior by D1- versus D2-expressing neurons is more nuanced than previously thought.

Kupchik YM, RM Brown, JA Heinsbroek, MK Lobo, DJ Schwartz and PW Kalivas. 2015. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections. Nature Neuroscience, 18: 1230-32.

Dr. Yoni Kupchik was a postdoctoral fellow who is now faculty at Hebrew University, Dr. Robyn Brown was a postdoctoral fellow at MUSC and is now at the Foley Neuroscience Institute in Melbourne, Jasper Heinsbroek is currently a Ph.D. candidate at MUSC, Dr. Mary Kay Lobo is a collaborator at the University of Maryland, and Ms Schwartz was a College of Charleston undergraduate conducting her research thesis.