The interactive effects of ketamine and ethanol on dopamine expression in the ventral tegmental area of rats.
Zhi-Bi Zhang, Tian-Yong Xu, Ding-Yun You, Shuai Yi, Qing Liu, Huifang-Jie Li, Jin-Yun Gu
Neuropsychiatric Disease and Treatment 2018 DOI: 10.2147/ndt.s163449 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ketamine Ethanol |
| Dose | 30 mg/kg and 60 mg/kg ketamine; 0.3156 g/kg ethanol |
| Topics | Ketamine Esketamine |
| Keywords | Ddc Dopamine Ethanol Ventral tegmental area |
| Key findings | Administering ketamine together with ethanol significantly increased dopamine concentration in the rat ventral tegmental area and was associated with differential regulation of mRNA for tyrosine hydroxylase, dopa decarboxylase, vesicular monoamine transporter 2, and synaptosomal-associated protein 25, plus changes in brain-derived neurotrophic factor protein. The authors propose that the rewarding properties of the combined drugs relate to dopaminergic neuron activation in this region. |
Abstract
A number of studies have demonstrated the significant and rapid antidepressant effects of ketamine, which is also known as a neurotoxic and illicit drug. Ketamine and alcohol are increasingly used together in clubs by teenagers and young adults. Previous studies have proven that chronic ketamine consumption induces a delayed and persistent activation of the dopamine (DA) system. However, the rewarding properties of recreational ketamine abuse remain unclear, and the underlying mechanisms of the effects on the DA system after administration of ketamine with ethanol are yet to be explored. Here, we evaluated the effects of two different doses of ketamine (30 mg/kg and 60 mg/kg) with and without ethanol (0.3156 g/kg) on DA concentration in the rat's ventral tegmental area (VTA), a vital region in the reward and motivation system. We explored the effects of the combined drug treatment on the expression profiling of the DA metabolism genes, tyrosine hydroxylase, dopa decarboxylase, vesicular monoamine transporter 2, and synaptosomal-associated protein 25, as well as protein expression level of brain-derived neurotrophic factor in the rat's VTA. We found that administration of ketamine with ethanol led to a significant increase of DA in the VTA associated with differential regulation of mRNA levels of the four DA metabolism genes and protein levels of brain-derived neurotrophic factor. Moreover, the rewarding properties of coadministration of ketamine and ethanol were related to dopaminergic neuron activation in the VTA. These results indicated the possibility that combined drug treatment might positively affect the mesencephalic DA reward system.
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 3
- Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment. Microscopy research and technique March 2012
- The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use. Emerging health threats journal April 15, 2011
- Journey through the K-hole: phenomenological aspects of ketamine use. Drug and Alcohol Dependence March 19, 2008