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Featured Research Papers

A figure from this month's paper.
A figure from this month's paper.

Featured Paper Archives
Featured paper of the Month!

August's Featured Paper!

Norepinephrine activates dopamine D4 receptors in the rat lateral habenula.

J Neurosci. 2015 Feb 25;35(8):3460-9.

David H. Root, Alexander F. Hoffman, Cameron H. Good, Shiliang Zhang, Eduardo Gigante, Carl R. Lupica, and Marisela Morales

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that 90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2(VMAT2)mRNA,and there is little coexpression ofTHandVMAT2protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function.

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

July's Featured Paper!

Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine Relapse

Biol Psychiatry. 2015 Jan 30. pii: S0006-3223(15)00045-1

Bryon Adinoff, Hong Gu, Carmen Merrick, Meredith McHugh, Haekyung Jeon-Slaughter, Hanzhang Lu, Yihong Yang, and Elliot A. Stein

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

June's Featured Paper!

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

Neuropsychopharmacology 2015 Jun;40(7):1762-71

Xiao-Fei Wang, Guo-Hua Bi, Yi He, Hong-Ju Yang, Jun-Tao Gao, Oluyomi M Okunola-Bakare, Rachel D Slack, Eliot L Gardner, Zheng-Xiong Xi, and Amy Hauck Newman

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

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Jordi Bonaventura.
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Hot off the Press Archives
Featured paper of the Month!

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

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.

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Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid

PNAS May 11, 2015, doi: 10.1073/pnas.1422001112

Shang-Yi A. Tsai, Michael J. Pokrass, Neal R. Klauer, Hiroshi Nohara, and Tsung-Ping Su

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Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation

Nat Neurosci. 2015 Apr 13. doi: 10.1038/nn.3998. [Epub ahead of print]

Dong V Wang, Hau-Jie Yau, Carl J Broker, Jen-Hui Tsou, Antonello Bonci, and Satoshi Ikemoto

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