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Pramipexole, a D3 receptor agonist, increases cortical gamma power and biochemical correlates of cortical excitation; implications for mood disorders
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  • Karli Gilbert,
  • Matthew Amontree,
  • Samantha Deasy,
  • Junfeng Ma,
  • Katherine Conant
Karli Gilbert
Georgetown University School of Medicine
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Matthew Amontree
Georgetown University School of Medicine
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Samantha Deasy
Georgetown University School of Medicine
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Junfeng Ma
Georgetown University School of Medicine
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Katherine Conant
Georgetown University

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Abstract

Major depressive disorder (MDD) has been associated with deficits in working memory as well as underlying gamma oscillation power. Consistent with this, overall reductions in cortical excitation have also been described with MDD. In previous work, we have demonstrated that the monoamine reuptake inhibitor venlafaxine increases gamma oscillation power in ex vivo hippocampal slices, and that this is associated with concomitant increases in pyramidal arbor and reduced levels of plasticity-restricting perineuronal nets (PNNs). In the present study we have examined effects of chronic treatment with pramipexole (PPX), a D3 dopamine receptor agonist, for its effects on gamma oscillation power as measured by in vivo electroencephalography (EEG) recordings in female BALB/c and C57Bl6 mice. We observe a modest but significant increase in 20-50 Hz gamma power with PPX in both strains. Additionally, biochemical analysis of prefrontal cortex lysates from PPX-treated BALB/c mice show a number of changes that could contribute to, or follow from, increased pyramidal excitability and/or gamma power. PPX-associated changes include reduced levels of specific PNN components as well as tissue inhibitor of matrix metalloproteases-1 (TIMP-1), which inhibits long term potentiation of synaptic transmission. Consistent with its effects on gamma power, PNN proteins and TIMP-1, chronic PPX treatment also improves working memory and reduces anhedonia. Together these results add to an emerging literature linking extracellular matrix and/or gamma oscillation power to both mood and cognition.
Submitted to European Journal of Neuroscience
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28 Jun 2024Review(s) Completed, Editorial Evaluation Pending