Dec 14, 2007

Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

Toxicology and Applied Pharmacology
Jing-Jer KeLung Yu

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 infus...Continue Reading

Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Presynaptic Terminals
Amphetamine
Exertion
Abnormal Degeneration
Neurologic Manifestations
6-Cyano-7-nitroquinoxaline-2,3-dione
Prefrontal Cortex
Body Parts - Cannula
Specimen Type - Cannula

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