Combinational effects of ketamine and amphetamine on behaviors and neurotransmitter systems of mice

Lai, Chuan-Ching; Lee, Li-Jen; Yin, Hsiang‐Shu

doi:10.1016/j.neuro.2013.04.014

Cited by 10 publications

(26 citation statements)

References 36 publications

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“…For every treatment, saline or Amph (5 mg/kg) was administered and immediately followed by saline or a low (10 mg/kg, LK) or high (50 mg/kg, HK) dose of Ket. Dosages of Amph and Ket and protocols of administration were based on our previous studies [12,21,22,25].…”

Section: Drug Treatmentsmentioning

confidence: 99%

“…Many human and animal studies have documented the synergistic actions of polydrug administration in behavioral [7,[10][11][12][13][14] and neurochemical [12,15,16] aspects. However, most studies, including ours, have examined the acute effects of combined drug treatments; the consequences of chronic repetitive administrations of multiple drugs, particularly in young subjects, have been studied less frequently.…”

Section: Introductionmentioning

confidence: 99%

“…Excessive NE and DA in the synaptic cleft could enhance synaptic transmission, which may lead to increased locomotor activity and stereotyped behaviors [19,20]. In addition, the GABAergic system is also modified by Ket or Amph in the motor cortex, somatosensory cortex, and striatum [12,21,22]. The key enzyme of GABA synthesis, glutamate decarboxylase 67 (GAD 67 ), is commonly used as a biomarker for GABAergic neurons, and certain properties of GAD 67 -positive cells are altered by Ket or Amph treatments [23,24].…”

Section: Introductionmentioning

confidence: 99%

“…In our previous study [12], we treated adult male mice with a single i.p. injection of saline, Amph (5 mg/kg), low Ket (LK, 10 mg/kg), high Ket (HK, 50 mg/kg), or Amph plus LK or HK (ALK or AHK) and examined the behavioral and neurochemical changes immediately after drug administration.…”

Section: Introductionmentioning

confidence: 99%

“…Interactive effects between Ket and Amph were evident. Ket exacerbated Amph-induced locomotion and stereotypy-like behaviors, and Amph exacerbated Ketinduced ataxia [12]. In the present study, we utilized behavioral and neurochemical approaches to explore the consequences of repetitive Ket and Amph administration in young adult mice.…”

Section: Introductionmentioning

confidence: 99%

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Behavioral and Neurochemical Changes Induced by Repetitive Combined Treatments of Ketamine and Amphetamine in Mice

2014

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The combined abuse of recreational drugs such as ketamine (Ket) and amphetamine (Amph) should be seriously considered important social and health issues. Numerous studies have documented the behavioral and neurochemical changes associated with polydrug administration; however, most studies have only examined the acute effects. The consequences following chronic repetitive polydrug use are less studied. In the present study, intraperitoneal injections of saline, Amph (5 mg/kg), low dose Ket (LK, 10 mg/kg), high dose Ket (HK, 50 mg/kg), or Amph plus LK or HK (ALK or AHK) were conducted twice a day for three consecutive days, and one final treatment was administered on day 4. After seven total treatments, animal behaviors, including locomotion, stereotypy and ataxia, were examined in a novel open field. The expression of GAD67 and dopamine (DA) levels were assessed in the striatum and motor-related cortices using immunohistochemistry and high-performance liquid chromatography. Drug-induced hyperactivities and Amph-mediated potentiation of Ket-triggered ataxia manifested after repeated drug treatments. A significant increase in the number of GAD67-positive puncta in the striatum and motor-related cortices was observed, suggesting a neural adaptive change in the GABAergic system. Four hours after the final treatment, while the behavioral hyperactivities had ceased, considerable changes were still evident in the motor-related cortices, suggesting modulation to the DAergic system. Together, our results show the interactive effects of these two drugs in behavioral and neurochemical aspects and neural adaptive changes in the GABAergic and DAergic systems.

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Section: Drug Treatmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Behavioral and Neurochemical Changes Induced by Repetitive Combined Treatments of Ketamine and Amphetamine in Mice

2014

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Alcohol aggravates ketamine-induced behavioral, morphological and neurochemical alterations in adolescent rats: The involvement of CREB-related pathways

Zuo

Liu

et al. 2018

Behavioural Brain Research

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The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders

2017

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Ketamine is a non-competitive antagonist at the N-methyl-d-aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute and chronic ketamine administration relative to a drug-free baseline or control condition. Systematic search of PubMed and PsychInfo electronic databases yielded 40 original peer-reviewed studies. There were sufficient rodent studies of the acute effects of ketamine at sub-anaesthetic doses for meta-analysis. Acute ketamine administration in rodents is associated with significantly increased dopamine levels in the cortex (Hedge’s g= 1.33, P<0.01), striatum (Hedge’s g=0.57, P<0.05) and the nucleus accumbens (Hedge’s g=1.30, P<0.05) compared to control conditions, and 62–180% increases in dopamine neuron population activity. Sub-analysis indicated elevations were more marked in in vivo (g=1.93) than ex vivo (g=0.50) studies. There were not enough studies for meta-analysis in other brain regions studied (hippocampus, ventral pallidum and cerebellum), or of the effects of chronic ketamine administration, although consistent increases in cortical dopamine levels (from 88 to 180%) were reported in the latter studies. In contrast, no study showed an effect of anaesthetic doses (>100 mg kg−1) of ketamine on dopamine levels ex vivo, although this remains to be tested in vivo. Findings in non-human primates and in human studies using positron emission tomography were not consistent. The studies reviewed here provide evidence that acute ketamine administration leads to dopamine release in the rodent brain. We discuss the inter-species variation in the ketamine induced dopamine release as well as the implications for understanding psychiatric disorders, in particular substance abuse, schizophrenia, and the potential antidepressant properties of ketamine, and comparisons with stimulants and other NMDA antagonists. Finally we identify future research needs.

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Combinational effects of ketamine and amphetamine on behaviors and neurotransmitter systems of mice

Cited by 10 publications

References 36 publications

Behavioral and Neurochemical Changes Induced by Repetitive Combined Treatments of Ketamine and Amphetamine in Mice

Behavioral and Neurochemical Changes Induced by Repetitive Combined Treatments of Ketamine and Amphetamine in Mice

Alcohol aggravates ketamine-induced behavioral, morphological and neurochemical alterations in adolescent rats: The involvement of CREB-related pathways

The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders

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