Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice.
Sun Mi Gu, Eunchong Hong, Sowoon Seo, Sanghyeon Kim, Seong Shoon Yoon, Hye Jin Cha, Jaesuk Yun
Journal of veterinary science September 1, 2024 DOI: 10.4142/jvs.23325 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mouse model |
| Intervention | GAD67 knockdown |
| Topics | Ketamine Esketamine |
| Keywords | Gad67 Jwh-018 Conditioned place preference Gamma-aminobutyric acid Ketamine addiction Neurotransmitters Drug dependence Brain chemistry Gaba signaling |
| Citations | 1 |
| Key findings | Knockdown of GAD67 in the dorsal striatum increased ketamine-induced conditioned place preference but did not affect JWH-018-induced conditioned place preference. |
Abstract
Glutamic acid decarboxylase 67 (GAD67) is a gamma-aminobutyric acid (GABA) synthesis enzyme associated with the function of other neurotransmitter receptors, such as the N-methyl-D-aspartate (NMDA) receptor and cannabinoid receptor 1. However, the role of GAD67 in the development of different abused drug-induced reward behaviors remains unknown. In order to elucidate the mechanisms of substance use disorder, it is crucial to study changes in biomarkers within the brain's reward circuit induced by drug use. The study was designed to examine the effects of the downregulation of GAD67 expression in the dorsal striatum on reward behavior development. We evaluated the effects of GAD67 knockdown on depression-like behavior and anxiety using the forced swim test and elevated plus maze test in a mouse model. We further determined the effects of GAD67 knockdown on ketamine- and JWH-018-induced conditioned place preference (CPP). Knockdown of GAD67 in the dorsal striatum of mice increased depression-like behavior, but it decreased anxiety. Moreover, the CPP score on the NMDA receptor antagonist ketamine was increased by GAD67 knockdown, whereas the administration of JWH-018, a cannabinoid receptor agonist, did not affect the CPP score in the GAD67 knockdown mice group compared with the control group. These results suggest that striatal GAD67 reduces GABAergic neuronal activity and may cause ketamine-induced NMDA receptor inhibition. Consequently, GAD67 downregulation induces vulnerability to the drug reward behavior of ketamine.
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 6
- Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & Therapeutics July 1, 2019
- Effect of Ketamine on Limbic GABA and Glutamate: A Human In Vivo Multivoxel Magnetic Resonance Spectroscopy Study Frontiers in Psychiatry September 8, 2020
- Pharmacology and adverse effects of new psychoactive substances: synthetic cannabinoid receptor agonists. Archives of Pharmacal Research April 2021
- Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential. Pharmacology, Biochemistry, and Behavior June 1, 2015
- Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice. Behavioural Pharmacology December 2014
and 1 more in the library