Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression.
Psychopharmacology (Berl)
; 233(19-20): 3647-57, 2016 Oct.
Article
in En
| MEDLINE
| ID: mdl-27488193
ABSTRACT
RATIONALE The N-methyl-D-aspartate (NMDA) receptor antagonists, including R-ketamine and rapastinel (formerly GLYX-13), show rapid antidepressant effects in animal models of depression. OBJECTIVE:
We compared the rapid and sustained antidepressant effects of R-ketamine and rapastinel in the social defeat stress model.RESULTS:
In the tail suspension and forced swimming tests, R-ketamine (10 mg/kg, intraperitoneal (i.p.)) or rapastinel (10 mg/kg, i.p.) significantly attenuated the increased immobility time in the susceptible mice, compared with the vehicle-treated group. In the sucrose preference test, both compounds significantly enhanced the reduced preference in susceptible mice 2, 4, or 7 days after a single injection. All mice were sacrificed 8 days after a single injection. Western blot analyses showed that R-ketamine, but not rapastinel, significantly attenuated the reduced brain-derived neurotrophic factor (BDNF)-TrkB signaling, postsynaptic density protein 95 (PSD-95), and GluA1 (a subtype of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor) in the prefrontal cortex, dentate gyrus, and CA3 of the hippocampus in the susceptible mice. In contrast, both compounds had no effect against the increased BDNF-TrkB signaling, PSD-95, and GluA1 seen in the nucleus accumbens of susceptible mice. Moreover, sustained antidepressant effect of R-ketamine (3 mg/kg, intravenous (i.v.)), but not rapastinel (3 mg/kg, i.v.), was detected 7 days after a single dose.CONCLUSIONS:
These results highlight R-ketamine as a longer lasting antidepressant compared with rapastinel in social defeat stress model. It is likely that synaptogenesis including BDNF-TrkB signaling in the prefrontal cortex (PFC) and hippocampus may be required for the mechanisms promoting this sustained antidepressant effect.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Stress, Psychological
/
Brain
/
Excitatory Amino Acid Antagonists
/
Brain-Derived Neurotrophic Factor
/
Ketamine
/
Antidepressive Agents
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Psychopharmacology (Berl)
Year:
2016
Document type:
Article
Affiliation country:
Japan