Co-Activation of Metabotropic Glutamate Receptor 3 and Beta-Adrenergic Receptors Modulates Cyclic-AMP and Long-Term Potentiation, and Disrupts Memory Reconsolidation.

Autor: Walker AG; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Sheffler DJ; Cancer Metabolism and Signaling Networks Program, Conrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Lewis AS; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Dickerson JW; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Foster DJ; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Senter RK; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Moehle MS; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Lv X; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Stansley BJ; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Xiang Z; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Rook JM; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA., Emmitte KA; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA.; Department of Chemistry, Vanderbilt University, Nashville, TN, USA., Lindsley CW; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA.; Department of Chemistry, Vanderbilt University, Nashville, TN, USA., Conn PJ; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2017 Dec; Vol. 42 (13), pp. 2553-2566. Date of Electronic Publication: 2017 Jun 30.
DOI: 10.1038/npp.2017.136
Abstrakt: Activation of β-adrenergic receptors (βARs) enhances both the induction of long-term potentiation (LTP) in hippocampal CA1 pyramidal cells and hippocampal-dependent cognitive function. Interestingly, previous studies reveal that coincident activation of group II metabotropic glutamate (mGlu) receptors with βARs in the hippocampal astrocytes induces a large increase in cyclic-AMP (cAMP) accumulation and release of adenosine. Adenosine then acts on A 1 adenosine receptors at neighboring excitatory Schaffer collateral terminals, which could counteract effects of activation of neuronal βARs on excitatory transmission. On the basis of this, we postulated that activation of the specific mGlu receptor subtype that mediates this response could inhibit βAR-mediated effects on hippocampal synaptic plasticity and cognitive function. Using novel mGlu receptor subtype-selective allosteric modulators along with knockout mice we now report that the effects of mGlu 2/3 agonists on βAR-mediated increases in cAMP accumulation are exclusively mediated by mGlu 3 . Furthermore, mGlu 3 activation inhibits the ability of the βAR agonist isoproterenol to enhance hippocampal LTP, and this effect is absent in slices treated with either a glial toxin or an adenosine A 1 receptor antagonist. Finally, systemic administration of the mGlu 2/3 agonist LY379268 disrupted contextual fear memory in a manner similar to the effect of the βAR antagonist propranolol, and this effect was reversed by the mGlu 3 -negative allosteric modulator VU0650786. Taken together, these data suggest that mGlu 3 can influence astrocytic signaling and modulate βAR-mediated effects on hippocampal synaptic plasticity and cognitive function.
Databáze: MEDLINE
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