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Both Ketamine and NBQX Attenuate Alcohol-Withdrawal Induced Depression in Male Rats

Bruk Getachew, Yousef Tizabi

Journal of Drug and Alcohol Research 2018 DOI: 10.4303/jdar/236069 (opens in new tab)

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AI-extracted from the abstract
Characteristics Preclinical animal study Peer reviewed
Population Adult male Wistar rats exposed to ethanol via inhalation chambers
Interventions Ketamine NBQX
Dose Ketamine 2.5 mg/kg; NBQX 5 mg/kg
Duration Ethanol exposure 4 h/day for 7 days; assessments 18 h after injections; sacrifice 2 h after behavioral tests
Measures Open field locomotor activity (OFLA), forced swim test (FST), hippocampal brain-derived neurotrophic factor (BDNF)
Topics Depression Esketamine Ketamine
Citations 17
Key points Alcohol withdrawal increased immobility in the forced swim test and reduced hippocampal BDNF in rats. Ketamine (2.5 mg/kg) and NBQX (5 mg/kg) each normalized both the swimming score and hippocampal BDNF, but combining the two drugs cancelled each other's effects. The authors suggest NMDA or AMPA/kainate receptor antagonists, acting at least partially through hippocampal BDNF, may have therapeutic potential in alcohol use disorder.

Abstract

The co-morbidity between heavy drinking and depression can negatively influence successful cessation of alcohol use. Since ketamine, a glutamatergic NMDA receptor antagonist, has shown promise as a quick-acting antidepressant, we studied its effects specifically on alcohol withdrawal-induced depression. We also evaluated the effects of NBQX an AMPA/kainate receptor antagonist, because some of the effects of ketamine are proposed to be indirectly mediated through these receptors. Adult male Wistar rats were exposed daily to ethanol via inhalation chambers 4 h/day for 7 days (blood alcohol concentration=160 mg%), followed by daily intraperitoneal injections of ketamine (2.5 mg/kg), NBQX (5mg/kg), alone or in combination. Eighteen hours later, open field locomotor activity (OFLA) followed by forced swim test (FST) were performed. The animals were sacrificed 2 h later for evaluation of brain-derived neurotrophic factor (BDNF) in the hippocampus. Alcohol withdrawal did not affect OFLA, but caused an increase in immobility in FST, suggesting induction of "depressive-like" helplessness. Both ketamine and NBQX normalized the swimming score in FST. The combination of the two drugs, however, cancelled each other's effect. Parallel to these behavioral observations, both ketamine and NBQX normalized the reduction in hippocampal BDNF caused by alcohol withdrawal. Here also, the combination of the two drugs cancelled each other's effect. These results suggest that either NMDA or AMPA/kainate receptor antagonists, acting at least partially through hippocampal BDNF, may be of therapeutic potential in alcohol use disorder.

Comparable studies

Other preclinical and animal studies on ketamine for depression, most cited first.

Study Year Design Participants
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Rats with spared nerve injury (neuropathic pain model), sham-operated rats, and control... 2011 Animal experimental study
Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress 2017 Preclinical animal study
Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression Susceptible mice in the social defeat stress model 2016 Animal experimental study
Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Wistar-Kyoto (WKY) rats and Wistar control rats 2020 Preclinical study

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