The Role of the Dopamine D5 Receptor and D1-D2 Receptor Heterooligomer Signalling in Rodent Prefrontal Cortex and Cognition
Year: 2015
Type: dissertation
Abstract: The dopamine D5 receptor is highly expressed in rodent prefrontal cortex (PFC) a region involved in cognition. We have previously shown that acute activation of the Gq-coupled dopamine D5 and D1-D2 receptor heteromer by the agonist SKF 83959 inhibited glycogen synthase kinase- 3 (GSK-3) activity in PFC, a protein that mediates cognitive performance in this region. Specifically, the dopamine D5 receptor suppressed GSK-3 activity through a mechanism dependent on brain-derived neurotrophic factor (BDNF) signaling, whereas inhibition of GSK-3 activity by D1-D2 heteromer appears to be independent of BDNF signaling in the PFC. We have demonstrated that SKF83959 improved cognitive performance in male rats using the egocentric learning task in the small Morris water maze. These studies potentially offer a novel therapeutic drug target to treat cognitive deficits in Alzheimer's disease and schizophrenia through activation of the dopamine D5 receptor signaling pathway involving increased BDNF signaling and inhibition of GSK-3 activity.
Source: TSpace (University of Toronto)
Author: David Pok Yik Yeung
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2613966267