{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang Y"],"funding":["the Penn State Hershey Neuroscience Institute; the Parkinson’s Disease Gift Fund of the Penn State Milton S. Hershey Medical Center","U.S. Department of Health &amp; Human Services | NIH | National Institute of Neurological Disorders and Stroke","NIMH NIH HHS","Brain and Behavior Research Foundation","NINDS NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Institute of Mental Health"],"pagination":["645-655"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9710464"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(2)"],"pubmed_abstract":["Dopamine D<sub>1</sub> agonists enhance cognition, but the role of different signaling pathways (e.g., cAMP or β-arrestin) is unclear. The current study compared 2-methyldihydrexidine and CY208,243, drugs with different degrees of both D<sub>1</sub> intrinsic activity and functional selectivity. 2-Methyldihydrexidine is a full agonist at adenylate cyclase and a super-agonist at β-arrestin recruitment, whereas CY208,243 has relatively high intrinsic activity at adenylate cyclase, but much lower at β-arrestin recruitment. Both drugs decreased, albeit in dissimilar ways, the firing rate of neurons in prefrontal cortex sensitive to outcome-related aspects of a working memory task. 2-Methyldihydrexidine was superior to CY208,243 in prospectively enhancing similarity and retrospectively distinguishing differences between correct and error outcomes based on firing rates, enhancing the micro-network measured by oscillations of spikes and local field potentials, and improving behavioral performance. This study is the first to examine how ligand signaling bias affects both behavioral and neurophysiological endpoints in the intact animal. The data show that maximal enhancement of cognition via D<sub>1</sub> activation occurred with a pattern of signaling that involved full unbiased intrinsic activity, or agonists with high β-arrestin activity."],"journal":["Molecular psychiatry"],"pubmed_title":["D1 dopamine receptors intrinsic activity and functional selectivity affect working memory in prefrontal cortex."],"pmcid":["PMC9710464"],"funding_grant_id":["Young Investigator Grant","R01 MH040537","R01 NS105471","U19 MH082441"],"pubmed_authors":["Lee SM","Yang Y","Mailman RB","Gowda K","Amin S","Imamura F"],"additional_accession":[]},"is_claimable":false,"name":"D1 dopamine receptors intrinsic activity and functional selectivity affect working memory in prefrontal cortex.","description":"Dopamine D<sub>1</sub> agonists enhance cognition, but the role of different signaling pathways (e.g., cAMP or β-arrestin) is unclear. The current study compared 2-methyldihydrexidine and CY208,243, drugs with different degrees of both D<sub>1</sub> intrinsic activity and functional selectivity. 2-Methyldihydrexidine is a full agonist at adenylate cyclase and a super-agonist at β-arrestin recruitment, whereas CY208,243 has relatively high intrinsic activity at adenylate cyclase, but much lower at β-arrestin recruitment. Both drugs decreased, albeit in dissimilar ways, the firing rate of neurons in prefrontal cortex sensitive to outcome-related aspects of a working memory task. 2-Methyldihydrexidine was superior to CY208,243 in prospectively enhancing similarity and retrospectively distinguishing differences between correct and error outcomes based on firing rates, enhancing the micro-network measured by oscillations of spikes and local field potentials, and improving behavioral performance. This study is the first to examine how ligand signaling bias affects both behavioral and neurophysiological endpoints in the intact animal. The data show that maximal enhancement of cognition via D<sub>1</sub> activation occurred with a pattern of signaling that involved full unbiased intrinsic activity, or agonists with high β-arrestin activity.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Feb","modification":"2025-04-05T09:43:50.494Z","creation":"2025-04-05T09:43:50.494Z"},"accession":"S-EPMC9710464","cross_references":{"pubmed":["30532019"],"doi":["10.1038/s41380-018-0312-1"]}}