title: Long term ketamine and ketamine plus alcohol toxicity - what can we learn from animal models?
abstract: This review addressed the adverse effects of the frequently-used recreational drug, ketamine through using mice and monkey models. Our laboratory has documented initially that ketamine can induce the formation of hyperphosphorlated tau (hypertau), which is a hallmark of Alzheimer's disease (AD), in the cerebral cortex of both mice and monkeys as well as apoptosis in neurons in these species. Besides the cerebral cortex, other centers in the central nervous system (CNS) and peripheral nervous system (PNS) are also influenced by ketamine. Cerebellum was found to be down-regulated in both mice and humans after long-term of ketamine administration and it was caused by the apoptosis of Purkinje cells. Deleterious effects in other organs reported in long-term ketamine users include of kidney dysfunction leading to proteinuria, fibrosis of the urinary bladder and reduction in size of the urinary bladder leading to frequent urination, increase of liver fibrosis and cardiac problems such as premature ventricular beats. Moreover, ketamine is usually co-administrated with other chemicals such as caffeine or alcohol. It has been reported increased harmful effects when ketamine was used in combination with the above substances. Mechanisms of damages of ketamine might be due to 1) up-regulation of NMDA receptors leading to overestimation of glutamatergic system or 2) the metabolite of ketamine which was a hydroquinone exerted toxicity.
authors.affiliation: Brain Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: M S M
authors.initials: MS
authors.lastname: Wai
authors.forename: P
authors.initials: P
authors.lastname: Luan
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: W M
authors.initials: WM
authors.lastname: Chan
authors.forename: T Y M
authors.initials: TY
authors.lastname: Tsui
authors.forename: H C
authors.initials: HC
authors.lastname: Tang
authors.forename: W P
authors.initials: WP
authors.lastname: Lam
authors.forename: M
authors.initials: M
authors.lastname: Fan
authors.forename: D T
authors.initials: DT
authors.lastname: Yew
mesh_terms: D000435:Alcoholic Intoxication / Q000150:complications*; D000778:Anesthetics, Dissociative / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D000882:Haplorhini; D007649:Ketamine / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine