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Featured paper of the Month!

February's Featured Paper!

Cocaine-Induced Endocannabinoid Mobilization in the Ventral Tegmental Area

Cell Rep. 2015 Sep 29;12(12):1997-2008

Huikun Wang, Tyler Treadway, Daniel P. Covey, Joseph F. Cheer, & Carl R. Lupica

Cocaine is a highly addictive drug that acts upon the brain’s reward circuitry via the inhibition of monoamine uptake. Endogenous cannabinoids (eCB) are lipid molecules released from midbrain dopamine (DA) neurons that modulate cocaine’s effects through poorly understood mechanisms. We find that cocaine stimulates release of the eCB, 2-arachidonoylglycerol (2-AG), in the rat ventral midbrain to suppress GABAergic inhibition of DA neurons, through activation of presynaptic cannabinoid CB1 receptors. Cocaine mobilizes 2-AG via inhibition of norepinephrine uptake and promotion of a cooperative interaction between Gq/11-coupled type-1 metabotropic glutamate and a1-adrenergic receptors to stimulate internal calcium stores and activate phospholipase C. The disinhibition of DA neurons by cocaine-mobilized 2-AG is also functionally relevant because it augments DA release in the nucleus accumbens in vivo. Our results identify a mechanism through which the eCB system can regulate the rewarding and addictive properties of cocaine.

You can read more about this paper at the website for PubMed.

January's Featured Paper!

High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice

J Med Chem. 2015 Aug 13;58(15):6195-213.

Comfort A. Boateng, Oluyomi M. Bakare, Jia Zhan, Ashwini K. Banala, Caitlin Burzynski, Elie Pommier, Thomas M. Keck, Prashant Donthamsetti, Jonathan A. Javitch, Rana Rais, Barbara S. Slusher, Zheng-Xiong Xi, and Amy Hauck Newman

You can read more about this paper at the website for PubMed.

December's Featured Paper!

Structure−Activity Relationships of (+)-Naltrexone-Inspired Toll-like Receptor 4 (TLR4) Antagonists

J Med Chem. 2015 Jun 25;58(12):5038-52.

Brandon R. Selfridge, Xiaohui Wang, Yingning Zhang, Hang Yin, Peter M. Grace, Linda R. Watkins, Arthur E. Jacobson, and Kenner C. Rice

You can read more about this paper at the website for PubMed.

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Hot off the Press Archives
Featured paper of the Month!

Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors

Nat Neurosci. 2015 Dec 7. doi: 10.1038/nn.4191.

Chun Yun Chang, Guillem R Esber, Yasmin Marrero-Garcia, Hau-Jie Yau, Antonello Bonci & Geoffrey Schoenbaum

Correlative studies have strongly linked phasic changes in dopamine activity with reward prediction error signaling. But causal evidence that these brief changes in firing actually serve as error signals to drive associative learning is more tenuous. Although there is direct evidence that brief increases can substitute for positive prediction errors, there is no comparable evidence that similarly brief pauses can substitute for negative prediction errors. In the absence of such evidence, the effect of increases in firing could reflect novelty or salience, variables also correlated with dopamine activity. Here we provide evidence in support of the proposed linkage, showing in a modified Pavlovian over-expectation task that brief pauses in the firing of dopamine neurons in rat ventral tegmental area at the time of reward are sufficient to mimic the effects of endogenous negative prediction errors. These results support the proposal that brief changes in the firing of dopamine neurons serve as full-fledged bidirectional prediction error signals.

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Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatinremodeling factors at the nuclear envelope

Proc Natl Acad Sci USA. 2015 Nov 9. pii: 201518894. [Epub ahead of print]

Shang-Yi A. Tsai, Jian-Ying Chuang, Meng-Shan Tsia, Xiao-fei Wang, Zheng-Xiong Xi, Jan-Jong Hung, Wen-Chang Chang, Antonello Bonci, and Tsung-Ping Su

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Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer

PNAS June 22, 2015, doi: 10.1073/pnas.1507704112

Jordi Bonaventura, Gemma Navarro, Verònica Casadó-Anguera, Karima Azdad, William Rea, Estefanía Moreno, Marc Brugarolas, Josefa Mallol, Enric I. Canela, Carme Lluís, Antoni Cortés, Nora D. Volkow, Serge N. Schiffmann, Sergi Ferré, and Vicent Casadó

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The National Institute on Drug Abuse (NIDA), is part of the National Institutes of Health (NIH), the principal biomedical and behavioral research agency of the United States Government. NIH is a component of the U.S. Department of Health and Human Services.

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