Effects of co-administration of ketamine and ethanol on the dopamine system via the cortex-striatum circuitry

Liu, Qing; Xu, Tian-Yong; Zhang, Zhi-Bi; Leung, Chi‐Kwan; You, Dingyun; Wang, Shangwen; Yi, Siyan; Qiang, Jun; Xie, Runfang; Li, Huifang-Jie; Zeng, Xiaofeng

doi:10.1016/j.lfs.2017.04.018

Cited by 8 publications

(13 citation statements)

References 54 publications

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“…However, the combined administration using a higher dose of ketamine (60 mg/kg) and 20% ethanol (K60+E) did not affect the DA concentration. These results correspond with our previous publication, in which a lower dose of ketamine (30 mg/kg) can synergistically interact with 20% ethanol to promote the DA release in the striatum, 6 and in present work, K30+E treatment significantly increased the DA concentration in the VTA.…”

Section: Resultssupporting

confidence: 93%

“… 25 Similarly, in vivo microdialysis experiments demonstrated that appetitive rewards promoted DA release in the NAc via the pathway receiving projections from the VTA. 26 From the present study, we noted a significant increase of DA concentration in the VTA after being treated with K30+E ( Figure 1 ), which correlated with our published findings that coadministration of 30 mg/kg ketamine and 20% ethanol elevated the DA concentration in the striatum of rats, 6 suggesting combined treatment of ketamine at a low dose and ethanol probably induced dopaminergic hyperactivity. However, few effects of ethanol on the alteration of the DA concentration were observed.…”

Section: Discussionsupporting

confidence: 91%

“…These findings indicates that coadministration of ketamine and ethanol clearly alters DDC expression in VTA, which differentiate the present study from our previous publication, in which the same treatment did not interfere DDC expression in PFC and striatum. 6 …”

Section: Resultsmentioning

confidence: 99%

“…These results were similar to our previous findings that combined treatment of ketamine at a high dose (60 mg/kg) with 20% ethanol promoted SNAP25 expression in the PFC, and other ketamine treatment with or without ethanol did not alter SNAP25 transcript levels. 6 , 8 …”

Section: Resultsmentioning

confidence: 99%

“… 5 Focusing on the DA system in rat brain, recently our group has shown that recreational ketamine abuse induces different regulation in the mRNA expression of four genes related to DA metabolism, especially for SNAP25, and protein function of BDNF in the cortex–striatum circuitry. 6 We found that significant increase of DA concentration in rats’ striatum could result in drug-paired place preference exhibited by ketamine and ethanol coadministration. However, upregulation of DA-related genes, SNAP25, was observed in the PFC of rats.…”

Section: Introductionmentioning

confidence: 87%

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The interactive effects of ketamine and ethanol on dopamine expression in the ventral tegmental area of rats

Zhang

Xu²,

You

et al. 2018

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BackgroundA 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.MethodsHere, 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.ResultsWe 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.ConclusionThese results indicated the possibility that combined drug treatment might positively affect the mesencephalic DA reward system.

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Section: Resultssupporting

confidence: 93%