Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system.
Fatemeh Khakpai, Mohaddeseh Ebrahimi-Ghiri, Sakineh Alijanpour, M. Zarrindast
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 1, 2019 DOI: 10.1016/j.biopha.2019.108717 (opens in new tab) via Semantic Scholar
Summary
AI-generated from the abstractKetamine, an NMDA antagonist, produced antidepressant-like effects in mice in the forced swimming test at doses of 5 and 10 mg/kg. Both CB1 and CB2 receptor drugs—ACPA (1 mg/kg), AM251 (1 mg/kg), GP1a (2 mg/kg), and AM630 (0.5 mg/kg)—also showed antidepressant action. Combining ineffective doses of ketamine with cannabinoid receptor antagonists resulted in antidepressant-like effects. None of the drug doses altered locomotor activity in the open-field test. The findings suggest a possible interaction between ketamine and the cannabinoid system in modulating depression-related behavior.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine ACPA AM251 GP1a AM630 |
| Dose | 5 and 10 mg/kg ketamine; 1 mg/kg ACPA; 1 mg/kg AM251; 2 mg/kg GP1a; 0.5 mg/kg AM630 |
| Keywords | Medicine |
| Key finding | Combining ineffective doses of ketamine with cannabinoid receptor antagonists produced antidepressant-like effects in mice. |
Abstract
The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses using the forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) in mice. Our results revealed that intra-peritoneal (i.p.) injection of ketamine (5 and 10 mg/kg), a non-competitive NMDA antagonist, dose-dependently produced antidepressant-like effect in the FST. Moreover, i.p. administration of both CB1 and CB2 receptor drugs: ACPA (1 mg/kg; CB1 receptor agonist), AM251 (1 mg/kg; CB1 receptor antagonist), GP1a (2 mg/kg; CB2 receptor agonist) and AM630 (0.5 mg/kg; CB2 receptor antagonist) exhibited antidepressant action. Interestingly, the concomitant administration of ineffective doses of ketamine and cannabinoid receptor antagonists provoked the antidepressant-like effects as compared to control group. It should be considered, all above mentioned doses of drugs could not change locomotor activity in the OFT. It seems that possible interaction between ketamine and cannabinoid system may modulate depression-related behavior.