Pramipexole, a D3 receptor agonist, increases cortical gamma power and
biochemical correlates of cortical excitation; implications for mood
disorders
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.