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Research ArticleNew Research, Disorders of the Nervous System

COMT Inhibition Alters Cue-Evoked Oscillatory Dynamics during Alcohol Drinking in the Rat

A. M. McCane, S. Ahn, L. L. Rubchinsky, S. S. Janetsian-Fritz, D. N Linsenbardt, C. L. Czachowski and C. C. Lapish
eNeuro 12 October 2018, 5 (5) ENEURO.0326-18.2018; https://doi.org/10.1523/ENEURO.0326-18.2018
A. M. McCane
1Department of Psychology, Indiana University Purdue University Indianapolis, IN 46202
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S. Ahn
2Department of Mathematics, East Carolina University, NC 27858
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L. L. Rubchinsky
3Department of Mathematical Sciences, Indiana University Purdue University Indianapolis, IN 46202
4Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202
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S. S. Janetsian-Fritz
1Department of Psychology, Indiana University Purdue University Indianapolis, IN 46202
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D. N Linsenbardt
1Department of Psychology, Indiana University Purdue University Indianapolis, IN 46202
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C. L. Czachowski
1Department of Psychology, Indiana University Purdue University Indianapolis, IN 46202
4Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202
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C. C. Lapish
1Department of Psychology, Indiana University Purdue University Indianapolis, IN 46202
4Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202
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  • Figure 1.
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    Figure 1.

    Voltage traces (1) and electrode placements (2) in the mPFC (A) and NA (B) during drinking trials. P rats (red) exhibit an augmented mPFC response to the CS (A1, inset) compared to Wistar rats (blue). All values are mean ± SEM. Bar depicts time when strains are different, p > 0.05.

  • Figure 2.
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    Figure 2.

    P rats consume more EtOH across sessions relative to Wistars (A) but do not differ in percentage of drinking trials (B). Overall movement velocities differ by strain for both drinking and non-drinking trials but both strains show a reduction in locomotor activity during drinking (C2) but not non-drinking trials (C1). All values are mean ± SEM; #p < 0.05, independent samples t test; *p < 0.05, main effect of strain.

  • Figure 3.
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    Figure 3.

    Theta oscillation are present in the 2CAP and are associated with drinking behaviors. Power spectral densities (A) in the mPFC (1) and NA (2) show a prominent peak in the θ frequency. Mean traces of mPFC-NA spectral coherence during non-drinking (1) and drinking (2) trials in Wistars (B) and P rats (C). Theta band wavelet coherence between the mPFC and NA for non-drinking (cyan, pink) and drinking (blue, red) trials in Wistars (D1) and P rats (D2); *p < 0.05 Bonferroni post hoc, drinking versus non-drinking.

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    Figure 4.

    Physiologic differences are observed in the phase domain. Phase synchrony between the mPFC (black) and NA (gray) before drinking (A1) and during drinking (A2) indicate oscillations are more in phase during drinking, relative to before drinking. The difference in phase during (purple) and before (orange) drinking (B). Histogram of phase difference during drinking trials, notice more pronounced peak at zero indicating more synchronized phases (C). Theta band synchrony index (γ) for Wistar (D1, E1) and P rats (D2, E2) before the CS (orange), during the US (purple), and after the US (green) over 15 non-drinking (D) and drinking trials (E). Values are mean ± SEM.

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    Figure 5.

    A pronounced phase reset is observed in the mPFC following presentation of the CS (A). MPFC and NA phase delay duration during non-drinking (B1) and drinking (B2) trials in Wistar (blue) and P rats (red). During non-drinking trials, there was no effect of the CS on the phase of the oscillation (B1). During drinking trials, P rats exhibit a greater CS-evoked phase delay in the mPFC, relative to Wistars (B2). There was no effect of the CS on phase delay in the NA. ITPC spectrograms (C) and phase coherence (D) for Wistar (1) and P rats (2). Both strains exhibit increases in ITPC following the CS; #p < 0.05, main effect of strain; *p < 0.05, Bonferroni post hoc, time different from baseline (200 ms before CS).

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    Figure 6.

    The behavioral and physiologic effects of tolcapone. Tolcapone decreases EtOH intake (A) in P rats but not Wistars and number of drinking trials in both strains (B). Tolcapone reduces mPFC-NA synchrony in Wistars (C); *p < 0.05, Bonferroni post hoc, main effect of treatment in P rats; #p < 0.05 main effect of treatment.

  • Figure 7.
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    Figure 7.

    The effects of tolcapone on the phase delay in Wistar (A1; blue) and P rats (A2; red) in the mPFC. Mean phase coherence (B) in Wistar (left) and P rats (right) under saline or tolcapone treatment. Tolcapone reduces the phase delay in P rats but not Wistars (A2). Tolcapone results in increased phase coherence following the CS in Wistars (B1) but not P rats (B2); #p < 0.05 Tukey’s HSD post hoc; *p < 0.05, time different from baseline.

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COMT Inhibition Alters Cue-Evoked Oscillatory Dynamics during Alcohol Drinking in the Rat
A. M. McCane, S. Ahn, L. L. Rubchinsky, S. S. Janetsian-Fritz, D. N Linsenbardt, C. L. Czachowski, C. C. Lapish
eNeuro 12 October 2018, 5 (5) ENEURO.0326-18.2018; DOI: 10.1523/ENEURO.0326-18.2018

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COMT Inhibition Alters Cue-Evoked Oscillatory Dynamics during Alcohol Drinking in the Rat
A. M. McCane, S. Ahn, L. L. Rubchinsky, S. S. Janetsian-Fritz, D. N Linsenbardt, C. L. Czachowski, C. C. Lapish
eNeuro 12 October 2018, 5 (5) ENEURO.0326-18.2018; DOI: 10.1523/ENEURO.0326-18.2018
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Keywords

  • alcohol preferring rat
  • tolcapone
  • θ oscillation
  • prefrontal cortex
  • nucleus accumbens
  • alcoholism
  • alcohol use disorder

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