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The GLP-1 receptor agonist liraglutide reverses mania-like alterations and memory deficits induced by D-amphetamine and augments lithium effects in mice: Relevance for bipolar disorder
- Source :
- Progress in Neuro-Psychopharmacology and Biological Psychiatry. 99:109872
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Metabolic and psychiatric disorders present a bidirectional relationship. GLP-1 system, known for its insulinotropic effects, has also been associated with numerous regulatory effects in cognitive and emotional processing. GLP-1 receptors (GLP-1R) agonists present neuroprotective and antidepressant/anxiolytic properties. However, the effects of GLP-1R agonism in bipolar disorder (BD) mania and the related cognitive disturbances remains unknown. Here, we investigated the effects of the GLP-1R agonist liraglutide (LIRA) at monotherapy or combined with lithium (Li) against D-amphetamine (AMPH)-induced mania-like symptoms, brain oxidative and BDNF alterations in mice. Swiss mice received AMPH 2 mg/kg or saline for 14 days. Between days 8–14, they received LIRA 120 or 240 μg/kg, Li 47.5 mg/kg or the combination Li + LIRA, on both doses. After behavioral evaluation the brain areas prefrontal cortex (PFC), hippocampus and amygdala were collected. AMPH induced hyperlocomotion, risk-taking behavior and multiple cognitive deficits which resemble mania. LIRA reversed AMPH-induced hyperlocomotion, working and recognition memory impairments, while Li + LIRA240 rescued all behavioral changes induced by AMPH. LIRA reversed AMPH-induced hippocampal oxidative and neurotrophic changes. Li + LIRA240 augmented Li antioxidant effects and greatly reversed AMPH-induced BDNF changes in PFC and hippocampus. LIRA rescued the weight gain induced by Li in the course of mania model. Therefore, LIRA can reverse some mania-like behavioral alterations and combined with Li augmented the mood stabilizing and neuroprotective properties of Li. This study points to LIRA as a promising adjunctive tool for BD treatment and provides the first rationale for the design of clinical trials investigating its possible antimanic effect.
- Subjects :
- Male
Agonist
medicine.medical_specialty
Bipolar Disorder
Dextroamphetamine
medicine.drug_class
Hippocampus
Lithium
Neuroprotection
Anxiolytic
Glucagon-Like Peptide-1 Receptor
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
Animals
Medicine
Prefrontal cortex
Amphetamine
Biological Psychiatry
Pharmacology
Memory Disorders
business.industry
Drug Synergism
Liraglutide
030227 psychiatry
Mania
Endocrinology
Antidepressant
Lipid Peroxidation
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 02785846
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Accession number :
- edsair.doi.dedup.....0bc7bce422c76c1d3bab045cc0749409