GLP‐1R Role in Cognition and Mood

Abstract

Major Depressive Disorder (MDD) is a common mental illness that often produces cognitive impairments in patients, hindering affected individuals from performing daily life activities. In 2016, 16.2 million adults had at least one episode of major depression and at least half of these patients also experienced cognitive impairments (National Survey on Drug Use and Health). Current pharmacotherapies for MDD are somewhat effective at treating the symptoms related to affect but are not effective in treating the cognitive impairments associated with MDD. A propitious answer to an effective antidepressant pharmacotherapy for both of these symptoms is being sought in glucagon-like peptide-1 receptor (GLP1-R) agonists. Activation of this receptor plays a role in some types of learning and memory and increases hippocampal neurogenesis, a critical component of antidepressant efficacy. We utilized location discrimination and progressive ratio tasks in laboratory mice to investigate spatial learning and memory and motivation, respectively, hypothesizing that GLP-1R activation would enhance execution of these tasks. Our results demonstrate that GLP-1R activation enhances cognitive performance in the location discrimination task in a sex-dependent manner and negatively affects the motivation measured in the progressive ratio task. These data indicate that GLP-1R has potential to treat cognitive impairments associated with MDD, but its role in improving motivational and mood aspects of MDD requires further investigation. Support or Funding Information Funding provided by R03 MH110749 (DLG), R21DA035588 (GDS), and FSU CRC Planning Grant (DLG), and the FSU College of Medicine. Systemic Ex-4 treatment enhances performance in the LD probe trials (A). Ex-4-treated males performed better in the easy probe trial (B), while Ex-4-treated females performed better in the difficult probe trial (C). *p<0.05 vs. respective SAL, N=11–12/group In females, direct administration of Ex-4 into the brain (icv) did not alter performance in the easy probe LD trial (A), but did improve performance in the more difficult probe test (B). *p<0.001, N=4/group In both sexes, administration of Ex-4 systemically (ip) tended to decrease the number of trials performed in the PR test, suggesting reduced motivation, but statistical significance was not observed. N=8/group. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.