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.
Animals
Bipolar Disorder
/ chemically induced
Dextroamphetamine
/ toxicity
Drug Synergism
Glucagon-Like Peptide-1 Receptor
/ agonists
Lipid Peroxidation
/ drug effects
Liraglutide
/ administration & dosage
Lithium
/ administration & dosage
Male
Mania
/ chemically induced
Memory Disorders
/ chemically induced
Mice
Bipolar disorder
Brain-derived neurotrophic factor (BDNF)
Cognitive impairment
D-amphetamine
GLP-1
Liraglutide
Mania
Oxidative stress
Journal
Progress in neuro-psychopharmacology & biological psychiatry
ISSN: 1878-4216
Titre abrégé: Prog Neuropsychopharmacol Biol Psychiatry
Pays: England
ID NLM: 8211617
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
18
07
2019
revised:
31
12
2019
accepted:
15
01
2020
pubmed:
20
1
2020
medline:
1
4
2021
entrez:
20
1
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31954756
pii: S0278-5846(19)30595-0
doi: 10.1016/j.pnpbp.2020.109872
pii:
doi:
Substances chimiques
Glucagon-Like Peptide-1 Receptor
0
Liraglutide
839I73S42A
Lithium
9FN79X2M3F
Dextroamphetamine
TZ47U051FI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109872Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no conflict of interests.