Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

Fraga, Daiane B.; Réus, Gislaine Z.; Abelaira, Helena M.; Luca, Renata D. De; Canever, Leila; Pfaffenseller, Bianca; Colpo, Gabriela D.; Kapczinski, Flávio; Quevedo, Joao L De; Zugno, Alexandra I.

doi:10.1590/1516-4446-2012-0858

Cited by 37 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors that primarily support the growth and survival of cholinergic, dopaminergic and motor neurons through its receptor tropomyosin receptor kinase B (TrkB) which is a tyrosine kinase receptor possessing tropomyosin-related kinase activity [10]. BDNF is synthesized by neurons in the frontal cortex and hippocampus of rodents [11,12,13] and regulates synaptic density [14] and cognition like memory and learning [15] which are the two parameters significantly affected in patients with schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Nardostachys jatamansi Targets BDNF-TrkB to Alleviate Ketamine-Induced Schizophrenia-Like Symptoms in Rats

Janardhanan

Sadanand²,

Vanisree³

2016

Neuropsychobiology

View full text Add to dashboard Cite

Objective: Schizophrenia, a common neurological disorder appearing in the late teens or early adulthood, is characterized by disorganized thinking, behaviour, and perception of emotions. Aberrant N-methyl-D-aspartate (NMDA) receptor-mediated synaptic plasticity is a major pathological event here due to dysfunction of dopamine and glutamate transmission at NMDA receptors. De-regulated brain-derived neurotrophic factor (BDNF), i.e., its signalling through the tropomyosin receptor kinase B (TrkB) receptor, is a major feature of schizophrenia. With recent global awareness of traditional plant medicines in reducing side effects, the aim of our study was to evaluate the efficacy of the ethanolic root extract of a herb belonging to the Valerianacea family, Nardostachys jatamansi, against ketamine-induced schizophrenia-like model in rats. Methods: The effect of the N. jatamansi drug (oral dosage of 500 mg/kg body weight for 14 days) in ketamine-administered male Wistar albino rats (30 mg/kg body weight for 5 days) on modulating behaviour and the level of neurotransmitters like dopamine and glutamate was studied in whole-brain homogenates, and its influence on BDNF and TrkB levels in 2 relevant brain regions, the hippocampus and prefrontal cortex, was assessed. Results: We observed that N. jatamansi treatment exhibited encouraging results in the modulation of ketamine-induced schizophrenia-like behaviours, principally the positive symptoms. Our drug both significantly upregulated the glutamate level and downregulated the dopamine level in whole-brain homogenates and retained the normal levels of BDNF (in the hippocampus but not in the prefrontal cortex) and TrkB (in both hippocampus and prefrontal cortex) induced by ketamine in rats. Conclusion: These findings suggest a neuroprotective effect of the ethanolic root extract of N. jatamansi against ketamine-induced schizophrenia-like symptoms in rats; possibly, regarding its effect on TrkB signalling. Further research is warranted in the treatment of schizophrenic symptoms.

show abstract

Section: Introductionmentioning

confidence: 99%

Nardostachys jatamansi Targets BDNF-TrkB to Alleviate Ketamine-Induced Schizophrenia-Like Symptoms in Rats

Janardhanan

Sadanand²,

Vanisree³

2016

Neuropsychobiology

View full text Add to dashboard Cite

show abstract

“…Autry et al found an increase in mouse hippocampal BDNF expression within 30 minutes of administration, but not at 24 hours (Autry et al, 2011). Fraga et al, in contrast, found a decrease in BDNF levels in rat hippocampus at one and six hours after the last injection though the animals had reduced immobility time at the six hour time point (Fraga et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice

et al. 2016

View full text Add to dashboard Cite

Ketamine has been shown to produce rapid and robust antidepressant effects in depressed individuals, however its abuse potential and adverse psychotomimetic effects limit its widespread use. Dextromethorphan may serve as a safer alternative based on pharmacodynamic similarities to ketamine. In this proof of concept study, behavioral and biochemical analyses were undertaken to evaluate the potential involvement of brain derived neurotrophic factor (BDNF) in the antidepressant-like effects of dextromethorphan in mice, with comparisons to ketamine and imipramine. Male Swiss, Webster mice were injected with dextromethorphan, ketamine or imipramine and their behaviors evaluated in the forced swim test (FST) and open field test. Western blots were used to measure brain derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, protein expression in the hippocampus and frontal cortex of these mice. Our results show dextromethorphan and imipramine each reduced immobility time in the FST without affecting locomotor activity, whereas ketamine reduced immobility time and increased locomotor activity. Ketamine also rapidly (within 40 min) increased pro-BDNF expression in an AMPA receptor-dependent manner in the hippocampus, while DM and imipramine did not alter pro-BDNF or BDNF levels in either the hippocampus or frontal cortex within this timeframe. These data demonstrate that dextromethorphan shares some features with both ketamine and imipramine. Additional studies looking at dextromethorphan may aid in the development of more rapid, safe, and efficacious antidepressant treatment.

show abstract

“…Low dose (2.5-10 mg/kg) ketamine can cause cognitive impairment, while lower doses (< 2.5 mg/kg) and a slightly higher dose (10-20 mg/kg) do not significantly affect cognition after 10 consecutive days of exposure (16). Some researchers have even used higher doses of ketamine (25 mg/kg) to study the effects on rats and found that they lead to positive and negative symptoms similar to schizophrenia as well as affect cognitive function (17). However, Imre et al (9), suggest that 4-16 mg/kg of ketamine is a subanesthetic dose for rodents, and 20-50 mg/kg is a high dose (18).…”

Section: Discussionmentioning

confidence: 99%

Ketamine Administration Leads to Learning-Memory Dysfunction and Decreases Serum Brain-Derived Neurotrophic Factor in Rats

Xie

Liu

et al. 2020

Front. Psychiatry

View full text Add to dashboard Cite

Objective: This study investigated the effects of acute or chronic ketamine administration on learning and memory function as well as levels of brain-derived neurotrophic factor (BDNF) in the hippocampus and blood in order to explore the potential correlation between learning-memory dysfunction and ketamine. Methods: Rats were treated with 25 mg/kg ketamine for 3 d (n = 20) or 14 d (n = 20). Saline-treated rats were used as controls. The Morris water maze test was used to evaluate spatial learning and memory after 10 d of withdrawal. The level of BDNF in serum and the hippocampus were measured by ELISA. Results: The number of platform crossings and residence time in the target platform quadrant were significantly reduced in ketamine 3 d and 14 d groups than in the saline controls (both p < 0.05). In addition, the average escape latency of ketamine 3 d and 14 d groups were significantly longer than that of the saline 3 d and 14 d groups (p < 0.0001), respectively. Further examination found that only serum samples from ketamine 14 d group showed significantly decreased BDNF level compared to that from saline 14 d groups (p < 0.05). However, no differences were detected in hippocampus samples. Conclusion: Chronic ketamine exposure (25 mg/kg) causes spatial learning and memory deficits in SD rats, which may be associated with decreased serum BDNF levels.

show abstract

Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

Cited by 37 publications

References 39 publications

Nardostachys jatamansi Targets BDNF-TrkB to Alleviate Ketamine-Induced Schizophrenia-Like Symptoms in Rats

Nardostachys jatamansi Targets BDNF-TrkB to Alleviate Ketamine-Induced Schizophrenia-Like Symptoms in Rats

Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice

Ketamine Administration Leads to Learning-Memory Dysfunction and Decreases Serum Brain-Derived Neurotrophic Factor in Rats

Contact Info

Product

Resources

About