Abstract
The hippocampus has a significant association with memory, cognition and emotions. The dopaminergic projections from both the ventral tegmental area and substantia nigra are thought to be involved in hippocampal activity. To date, however, few studies have investigated dopaminergic innervation in the hippocampus or the functional consequences of reduced dopamine in disease models. Further complicating this, the hippocampus exhibits anatomical and functional differentiation along its dorso-ventral axis. In this work we investigated the role of dopamine on hippocampal long term potentiation using D-amphetamine, which stimulates dopamine release, and also examined how a dopaminergic lesion affects the synaptic transmission across the anatomic subdivisions of the hippocampus. Our findings indicate that a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine induced dopaminergic lesion has time-dependent effects and impacts mainly on the ventral region of the hippocampus, consistent with the density of dopaminergic innervation. Treatment with a preferential D3 receptor agonist pramipexole partly restored normal synaptic transmission and Long-Term Potentiation. These data suggest a new mechanism to explain some of the actions of pramipexole in Parkinson´s disease.
Highlights
IntroductionThat DA and its regulation may be important in variety of hippocampal functions
It is likely, that DA and its regulation may be important in variety of hippocampal functions
I/O curves and Paired Pulse Facilitation (PPF) ratio were recorded before high frequency stimulation
Summary
That DA and its regulation may be important in variety of hippocampal functions. We demonstrate that pharmacological elevation of DA with Amph results in an increase in LTP, depression of the Input/Output (I/O) curve and an augmentation in Paired Pulse Facilitation (PPF) ratio under both baseline and MPTP lesion conditions These effects were consistent across the hippocampus, larger in vHip than dHip. PPX treatment succeeded in restoring the already depressed I/O curve of MPTP-lesioned mice and increased LTP and reduced the PPF ratio in vHip. PPX treatment succeeded in restoring the already depressed I/O curve of MPTP-lesioned mice and increased LTP and reduced the PPF ratio in vHip These findings provide insight into the cognitive deficits and mood disorders that affect Parkinson’s Disease patients and partially explain the antidepressant properties previously described for PPX
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