Activation of ventral hippocampal CB1 receptors inhibits ketamine-induced anxiogenic-like behavior: Alteration of BDNF/c-Fos levels in the mouse hippocampus.
Sakineh Alijanpour, Ameneh Rezayof
Brain Research April 1, 2023 DOI: 10.1016/j.brainres.2023.148378 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Male NMRI mice |
| Interventions | Ketamine ACPA |
| Dose | ketamine 5-20 mg/kg (i.p.); ketamine 10 mg/kg (i.p.); ACPA 0.5-4 ng/mouse |
| Measures | elevated plus-maze (EPM), western blotting |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine (5-20 mg/kg, i.p.) produced anxiety-like behavior in the elevated plus-maze and increased hippocampal BDNF and c-Fos levels. Activating ventral hippocampal CB1 receptors with ACPA (0.5-4 ng/mouse) blocked ketamine's anxiety-like effects and reduced hippocampal BDNF and c-Fos, suggesting cannabinoid receptor agonists may have therapeutic potential for ketamine-induced anxiety-related responses. |
Abstract
Considering the increasing usage of ketamine as a recreational drug with hallucinogenic properties and also scarce studies about receptor systems responsible for its effects, in the present study we aimed to investigate whether the activation of the ventral hippocampal (VH) CB1 cannabinoid receptors affects the anxiety-like behaviors induced by ketamine. Also, the levels of BDNF and c-Fos proteins in the mouse hippocampus were measured following the treatments. For this purpose, male NMRI mice were cannulated bilaterally in the VH with a stereotaxic apparatus. Anxiety properties and protein changes were measured using elevated plus-maze (EPM) and western blotting respectively. The results revealed that intraperitoneal (i.p.) administration of ketamine (5-20 mg/kg) significantly decreased the percentage of open arm time (%OAT) and open arm entry (%OAE) in the EPM with no alteration in the locomotor activity suggesting an anxiogenic-like behavior to ketamine. Furthermore, ketamine administration (10 mg/kg, i.p.) increased BDNF and c-Fos levels in the hippocampus. Interestingly, activation of the VH CB1 receptors by ACPA (0.5-4 ng/mouse) inhibited the anxiogenic-like behaviors produced by ketamine, whereas the microinjection of the same doses of ACPA into VH by itself had no effect on the EPM parameters. Hippocampal levels of BDNF and c-Fos decreased after treatment with combined ketamine with ACPA. These results suggest the therapeutic potency of cannabinoid receptor agonists for ketamine-induced anxiogenic-related responses. This effect might be at least partially mediated by the alteration of BDNF and c-Fos signaling in the hippocampus.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 15
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Brain-Derived Neurotrophic Factor and Initial Antidepressant Response to anN-Methyl-D-Aspartate Antagonist The Journal of Clinical Psychiatry September 8, 2009
- Ketamine administration reduces amygdalo‐hippocampal reactivity to emotional stimulation Human Brain Mapping February 25, 2016
- Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 1, 2019
and 10 more in the library