Prenatal ketamine exposure impairs prepulse inhibition via arginine vasopressin receptor 1A-mediated GABAergic neuronal dysfunction in the striatum.
Aeseul Kim, Sun Mi Gu, Haemiru Lee, Dong Eun Kim, Jin Tae Hong, Jaesuk Yun, Hye Jin Cha
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 1, 2023 DOI: 10.1016/j.biopha.2023.114318 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Pregnant F344 rats and their offspring |
| Interventions | ketamine methoxetamine |
| Topics | Esketamine Ketamine |
| Keywords | Methoxetamine N-methyl-d-aspartate receptor Prepulse inhibition Δ-aminobutyric acid |
| Citations | 5 |
| Key findings | Prenatal NMDA receptor antagonist treatment induces GABAergic neuronal dysfunction and abnormalities in sensorimotor gating via regulating Avpr1a expression in the striatum. |
Abstract
Ketamine is a widely used anesthetic with N-methyl-D-aspartate (NMDA) receptor antagonism. Exposure to ketamine and NMDA receptor antagonists may induce psychosis. However, the mechanism underlying the effects of ketamine on the immature brain remains unclear. In this study, NMDA receptor antagonists, ketamine and methoxetamine, were administered to pregnant F344 rats (E17). These regimens induce psychosis-like behaviors in the offspring, such as hyperlocomotion induced by MK-801, a non-competitive NMDA receptor antagonist. We also observed that prepulse inhibition (PPI) was significantly reduced. Interestingly, ketamine administration increased the arginine vasopressin receptor 1A (Avpr1a) expression levels in the striatum of offspring with abnormal behaviors. Methoxetamine, another NMDA receptor antagonist, also showed similar results. In addition, we demonstrated a viral vector-induced Avpr1a overexpression in the striatum-inhibited PPI. In the striatum of offspring, ketamine or methoxetamine treatment increased glutamate decarboxylase 67 (GAD67) and δ-aminobutyric acid (GABA) levels. These results show that prenatal NMDA receptor antagonist treatment induces GABAergic neuronal dysfunction and abnormalities in sensorimotor gating via regulating Avpr1a expression in the striatum.
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 8
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry April 5, 2017
- Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine Human Psychopharmacology: Clinical and Experimental March 1, 2012
- Methoxetamine (MXE) – A Phenomenological Study of Experiences Induced by a “Legal High” from the Internet Journal of Psychoactive Drugs July 1, 2013
- Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant. Neuroscience Bulletin December 2016
and 3 more in the library