Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol.

Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Research Abstract Details 

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Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Abstract Text:

Taku Nagai,Kazuhiro Takuma,Misato Dohniwa,Daisuke Ibi,Hiroyuki Mizoguchi,Hiroyuki Kamei,Toshitaka Nabeshima,Kiyofumi Yamada,Taku Nagai,Kazuhiro Takuma,Misato Dohniwa,Daisuke Ibi,Hiroyuki Mizoguchi,Hiroyuki Kamei,Toshitaka Nabeshima,Kiyofumi Yamada,

RATIONALE: Although chronic use of methamphetamine (METH) leads to long-lasting cognitive dysfunction in humans, there are few reports about an animal model that reflects METH-induced impairment of working memory. OBJECTIVES: In this study, we investigated the effect of repeated METH treatment on spatial working memory in rats. MATERIALS AND METHODS: Rats were repeatedly administered METH (2 mg/kg) once a day for 7 days, and their memory function was assessed with a delayed spatial win-shift task in a radial arm maze. The task consisted of two phases, a training phase and a test phase, separated by a delay. RESULTS: METH-treated animals showed an impairment of performance in the test phase when the delay time was increased from 5 to 30 min or longer. The effect of METH persisted for at least 14 days after the drug withdrawal. METH-induced impairment of working memory was reversed by clozapine (3 and 10 mg/kg, for 7 days), but not haloperidol (1 and 2 mg/kg, for 7 days). The improving effect of clozapine diminished 7 days after the withdrawal. Phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) levels were significantly increased in the hippocampus of saline-treated control rats from 5 to 60 min after the training phase. In contrast, hyperphosphorylation of ERK1/2 was abolished in the hippocampus of rats treated with METH. CONCLUSIONS: These findings suggest that repeated METH treatment induces impairment of working memory, which is associated with a dysfunctional ERK1/2 pathway in the hippocampus. Furthermore, clozapine may be effective for the treatment of METH-induced cognitive dysfunction.

Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Publishing Authors By Initials

T Nagai,K Takuma,M Dohniwa,D Ibi,H Mizoguchi,H Kamei,T Nabeshima,K Yamada,T Nagai,K Takuma,M Dohniwa,D Ibi,H Mizoguchi,H Kamei,T Nabeshima,K Yamada,

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Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Psychopharmacology

VOLUME: 194

Page Numbers: 21-32

Journal Abbreviation: Psychopharmacology (Berl.)

ISSN: 0033-3158

DAY: 20

MONTH: 05

YEAR: 2007

Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Information

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LANGUAGE: eng

NlmUniqueID: 7608025

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AFFILIATION: Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.

Country: Germany

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MEDLINETA: Psychopharmacology (Berl)

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