Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

Jing Jer Ke, Hsiun Ing Chen, Chauying J. Jen, Yu-Min Kuo, Chianfang G. Cherng, Yen Ping N Tsai, Ming Che Ho, Chia Wen Tsai, Lung Yu

Research output: Contribution to journalArticle

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Abstract

We hereby report that repeated administration of ketamine (350 mg/kg in total) and methamphetamine (30 mg/kg in total) causes specific glutamatergic and dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine did not affect basal body temperature or the later methamphetamine-induced hyperthermia. However, pretreatment with repeated doses of ketamine aggravated methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine transporter density as well as poor gait balance performance. In contrast, methamphetamine-induced serotonergic depletion was not altered by ketamine pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated the ketamine-induced glutamatergic damage as indicated by reduced levels of the vesicular glutamate transporter in hippocampus and striatum and poor memory performance in the Morris water maze. Finally, since activation of the D1 and AMPA/kainate receptors has been known to be involved in the release of glutamate and dopamine, we examined the effects of co-administration of SCH23390, a D1 antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion abolished ketamine's potentiation of methamphetamine-induced dopamine neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of ketamine potentiate methamphetamine-induced dopamine neurotoxicity via AMPA/kainate activation and that conjunctive use of methamphetamine aggravates ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation.

Original languageEnglish
Pages (from-to)239-247
Number of pages9
JournalToxicology and Applied Pharmacology
Volume227
Issue number2
DOIs
Publication statusPublished - 2008 Mar 1

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Methamphetamine
Ketamine
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
6-Cyano-7-nitroquinoxaline-2,3-dione
Dopamine
Kainic Acid
Chemical activation
Vesicular Glutamate Transport Proteins
Intraventricular Infusions
Kainic Acid Receptors
3,4-Dihydroxyphenylacetic Acid
Dopamine Agents
Dopamine Plasma Membrane Transport Proteins
Induced Hyperthermia
AMPA Receptors
Dopaminergic Neurons
Body Temperature
Gait
Neurons
Toxicity

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

Ke, Jing Jer ; Chen, Hsiun Ing ; Jen, Chauying J. ; Kuo, Yu-Min ; Cherng, Chianfang G. ; Tsai, Yen Ping N ; Ho, Ming Che ; Tsai, Chia Wen ; Yu, Lung. / Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine. In: Toxicology and Applied Pharmacology. 2008 ; Vol. 227, No. 2. pp. 239-247.
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Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine. / Ke, Jing Jer; Chen, Hsiun Ing; Jen, Chauying J.; Kuo, Yu-Min; Cherng, Chianfang G.; Tsai, Yen Ping N; Ho, Ming Che; Tsai, Chia Wen; Yu, Lung.

In: Toxicology and Applied Pharmacology, Vol. 227, No. 2, 01.03.2008, p. 239-247.

Research output: Contribution to journalArticle

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