Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration.
Animals
Anxiety
/ pathology
Behavior, Animal
Brain-Derived Neurotrophic Factor
/ metabolism
Cell Nucleus
/ metabolism
Disease Models, Animal
Female
Green Fluorescent Proteins
/ metabolism
Hippocampus
/ metabolism
Ketamine
/ administration & dosage
Male
Memory, Episodic
Mice, Transgenic
Neurons
/ metabolism
Recombination, Genetic
Sex Characteristics
Social Behavior
BDNF
activated neurons
antidepressant
behavior
hydroxynorketamine
ketamine
rapid-acting
sex difference
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
20 Mar 2020
20 Mar 2020
Historique:
received:
31
01
2020
revised:
13
03
2020
accepted:
17
03
2020
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
6
1
2021
Statut:
epublish
Résumé
Rapid-acting antidepressants ketamine and (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) have overcome some of the major limitations of classical antidepressants. However, little is known about sex-specific differences in the behavioral and molecular effects of ketamine and (2R,6R)-HNK in rodents. We treated mice with an intraperitoneal injection of either saline, ketamine (30 mg kg Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in sociability and anxiety tests. Moreover, ketamine and (2R,6R)-HNK had opposite effects in the forced swim test (FST) depending on gender. In addition, in male mice, ketamine-treated animals were less immobile compared to (2R,6R)-HNK, thus showing a different profile of the two drugs in the FST. At the molecular level we identified Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in social and anxiety behavior and a different pattern between ketamine and (2R,6R)-HNK in the FST in male and female mice. At the molecular level, female mice treated with ketamine showed an increase of
Sections du résumé
BACKGROUND
BACKGROUND
Rapid-acting antidepressants ketamine and (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) have overcome some of the major limitations of classical antidepressants. However, little is known about sex-specific differences in the behavioral and molecular effects of ketamine and (2R,6R)-HNK in rodents.
METHODS
METHODS
We treated mice with an intraperitoneal injection of either saline, ketamine (30 mg kg
RESULTS
RESULTS
Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in sociability and anxiety tests. Moreover, ketamine and (2R,6R)-HNK had opposite effects in the forced swim test (FST) depending on gender. In addition, in male mice, ketamine-treated animals were less immobile compared to (2R,6R)-HNK, thus showing a different profile of the two drugs in the FST. At the molecular level we identified
CONCLUSION
CONCLUSIONS
Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in social and anxiety behavior and a different pattern between ketamine and (2R,6R)-HNK in the FST in male and female mice. At the molecular level, female mice treated with ketamine showed an increase of
Identifiants
pubmed: 32244978
pii: ijms21062142
doi: 10.3390/ijms21062142
pmc: PMC7139539
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Green Fluorescent Proteins
147336-22-9
Ketamine
690G0D6V8H
6-hydroxynorketamine
81395-70-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Sundhed og Sygdom, Det Frie Forskningsråd
ID : 5053-00103A
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1193
Organisme : NARSAD Brain and Behaviour Foundation, USA
ID : 22752
Organisme : Boehringer Ingelheim Stiftung
ID : BIS09
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