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Featured Research Papers

Doctor Zuzana Justinova.
Doctor Zuzana Justinova.

Featured Paper Archives
Featured paper of the Month!

September's Featured Paper!

Differential Effects of Presynaptic versus Postsynaptic Adenosine A2A Receptor Blockade onΔ9-Tetrahydrocannabinol (THC) Self-Administration in Squirrel Monkeys

J Neurosci. 2014 May 7;34(19):6480-4.

Zuzana Justinova, Godfrey H. Redhi, Steven R. Goldberg, and Sergi Ferre

Different doses of an adenosine A2A receptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl)ethenyl]-7 methyl-3-[3-(phosphooxy)propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A2A receptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynapticA2A receptors localized in striatopallidal neurons. This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A2A receptor antagonists SCH-442416 [2-(2-furanyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] and KW-6002 [(E)-1, 3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously selfadminister THC. SCH-442416 produced a significant shift to the right of the THC self-administration dose–response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW-6002 produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A2A receptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC.

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

August's Featured Paper!

Gangliosides and Ceramides Change in a Mouse Model of Blast Induced Traumatic Brain Injury

ACS Chem. Neurosci., 2013, 4 (4), pp 594–600

Amina S. Woods, Benoit Colsch, Shelley N. Jackson, Jeremy Post, Kathrine Baldwin, Aurelie Roux, Barry Hoffer, Brian M. Cox, Michael Hoffer, Vardit Rubovitch, Chaim G. Pick, J. Albert Schultz, and Carey Balaban.

You can read more about this paper at the website for ASC Chemical Neuroscience.

July's Featured Paper!

Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]-acetamide (Modafinil) Analogues

J Med Chem 2014, 57, 1000-1013

Oluyomi M. Okunola-Bakare, Jianjing Cao, Theresa Kopajtic, Jonathan L. Katz, Claus J. Loland, Lei Shi, and Amy Hauck Newman.

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

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Dr. Federica Lucantonio.
Dr. Federica Lucantonio.

Hot off the Press Archives
Featured paper of the Month!

Orbitofrontal activation restores insight lost after cocaine use

Nature Neuroscience (2014) doi:10.1038/nn.3763

Federica Lucantonio, Yuji K Takahashi, Alexander F Hoffman, Chun Chang, Sheena Bali-Chaudhary, Yavin Shaham, Carl R Lupica, & Geoffrey Schoenbaum

Addiction is characterized by a lack of insight into the likely outcomes of one’s behavior. Insight, or the ability to imagine outcomes, is evident when outcomes have not been directly experienced. Using this concept, work in both rats and humans has recently identified neural correlates of insight in the medial and orbital prefrontal cortices. We found that these correlates were selectively abolished in rats by cocaine self-administration. Their abolition was associated with behavioral deficits and reduced synaptic efficacy in orbitofrontal cortex, the reversal of which by optogenetic activation restored normal behavior. These results provide a link between cocaine use and problems with insight. Deficits in these functions are likely to be particularly important for problems such as drug relapse, in which behavior fails to account for likely adverse outcomes. As such, our data provide a neural target for therapeutic approaches to address these defining long-term effects of drug use.

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Orbitofrontal neurons infer the value and identity of predicted outcomes

Nature Communications 5:3926 | DOI: 10.1038/ncomms4926

Thomas A. Stalnaker, Nisha K. Cooch, Michael A. McDannald, Tzu-Lan Liu, Heather Wied, & Geoffrey Schoenbaum

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Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

J. Neurosci June 4, 2014 - 34(23):7754–7762

Eugene A. Kiyatkin, Albert H. Kim, Ken T. Wakabayashi, Michael H. Baumann, and Yavin Shaham

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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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