Browsing by Subject "AMPA receptors"

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    Synergy of AMPA and NMDA Receptor Currents in Dopaminergic Neurons: A Modeling Study
    (Frontiers Media SA, 2016) Zakharov, Denis; Lapish, Christopher; Gutkin, Boris; Kuznetsov, Alexey; Department of Psychology, School of Science
    Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co-activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency.
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    Systemic Administration of the AMPA Receptor Antagonist, NBQX, Reduces Alcohol Drinking in Male C57BL/6J, but not Female C57BL/6J or High Alcohol Preferring (HAP) Mice
    (Wiley, 2020-11) Bauer, Meredith R.; Garcy, Daniel P.; Boehm, Stephen L., II.; Psychology, School of Science
    Background: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are ionotropic glutamate receptors that have been investigated for their role in modulating alcohol consumption. However, little is known about the role of AMPA receptors in the control of binge-like or free-access alcohol drinking in C57BL/6J or in selectively bred high-alcohol-preferring (HAP) mice. The purpose of this experiment was to assess the role of systemic administration of the AMPA receptor antagonist, 2,3-dioxo-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), on alcohol consumption using a model of binge-like drinking, drinking in the dark (DID) and free-access 2-bottle choice (2BC) in male and female C57BL/6J and HAP mice. Methods: C57BL/6J mice were allowed free access to 20% (v/v) alcohol for 2 hours each day beginning 3 hours into the dark cycle for 4 days. On day 5, mice were intraperitoneally injected with one of 4 doses of NBQX (0, 3, 10, or 30 mg/kg; n = 10) 15 minutes before alcohol presentation and were given 4-hour alcohol access (extended DID). HAP mice were given 24-hour free access to 10% (v/v) alcohol and water for 19 days. On day 20, mice were intraperitoneally injected with one of 4 doses of NBQX (0, 3, 10, or 30 mg/kg; n = 9) 15 minutes before alcohol and water presentation. Results: In the first 2 hours of DID, at 30 mg/kg, male, but not female C57BL/6J or HAP, mice drank significantly less alcohol compared with controls and 30 mg/kg NBQX did not alter saccharin intake in the males. Although male HAP mice drank significantly less alcohol than female mice following 10 mg/kg NBQX, neither sex exhibited drinking that differed significantly from controls. NBQX did not reduce locomotor behavior at any dose, sex, or genotype. Conclusions: These data suggest that AMPA receptors play a key role in modulating binge-like alcohol consumption without altering saccharin consumption or general locomotion and that this effect is specific to sex and genotype.