title: Pramipexole restores depressed transmission in the ventral hippocampus following MPTP-lesion.
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 D3receptor 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.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria 3052, Australia.
authors.forename: Javier
authors.initials: J
authors.lastname: Castro-Hernández
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria 3052, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria 3052, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D052160:Benzothiazoles / Q000008:administration & dosage*; D003913:Dextroamphetamine / Q000008:administration & dosage; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077487:Pramipexole; D013378:Substantia Nigra / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013702:Temporal Lobe / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects
chemical_list: D052160:Benzothiazoles; D000077487:Pramipexole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003913:Dextroamphetamine; D004298:Dopamine