Galantamine ameliorates the impairment of recognition memory in mice repeatedly treated with methamphetamine: involvement of allosteric potentiation of nicotinic acetylcholine receptors and dopaminergic-ERK1/2 systems

被引：52

作者：

Noda, Yukihiro ^{[1
]}

Mouri, Akihiro ^{[2
]}

Ando, Yu ^{[1
]}

Waki, Yukari ^{[1
]}

Yamada, Shin-Nosuke ^{[1
]}

Yoshimi, Akira ^{[1
,3
]}

Yamada, Kiyofumi ^{[3
]}

Ozaki, Norio ^{[4
]}

Wang, Dayong ^{[2
]}

Nabeshima, Toshitaka ^{[2
]}

机构：

[1] Meijo Univ, Grad Sch Pharmaceut Sci, Div Clin Sci & Neuropsychopharmacol, Nagoya, Aichi, Japan

[2] Meijo Univ, Grad Sch Pharmaceut Sci, Dept Chem Pharmacol, Nagoya, Aichi, Japan

[3] Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Nagoya, Aichi 4648601, Japan

[4] Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi 4648601, Japan

来源：

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY | 2010年 / 13卷 / 10期

基金：

日本学术振兴会;

关键词：

Allosteric potentiation of nicotinic acetylcholine receptors; cognitive impairment; dopamine; extracellular signal-regulated kinase 1/2; galantamine; methamphetamine; PREFRONTAL CORTEX; DOPAMINE-RECEPTORS; SCHIZOPHRENIA; ACTIVATION; PATHWAY; NEUROTRANSMISSION; PHENCYCLIDINE; DYSFUNCTION; INHIBITION; ABSTINENCE;

D O I：

10.1017/S1461145710000222

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Galantamine, a drug used to treat Alzheimer's disease, inhibits acetylcholinesterase (AChE) and allosterically modulates nicotinic acetylcholine receptors (nAChRs) resulting in stimulation of catecholamine neurotransmission. In this study, we investigated whether galantamine exerts cognitive-improving effects through the allosteric modulation of nAChRs in an animal model of methamphetamine (Meth) psychosis. The mice treated with Meth (1 mg/kg.d) for 7 d showed memory impairment in a novel object recognition test. Galantamine (3 mg/kg) ameliorated the memory impairment, and it increased the extracellular dopamine release in the prefrontal cortex (PFC) of Meth-treated mice. Donepezil, an AChE inhibitor (1 mg/kg) increased the extracellular ACh release in the PFC, whereas it had no effect on the memory impairment in Meth-treated mice. The nAChR antagonist, mecamylamine, and dopamine D(1) receptor antagonist, SCH 23390, blocked the ameliorating effect of galantamine on Meth-induced memory impairment, whereas the muscarinic AChR antagonist, scopolamine, had no effect. The effects of galantamine on extracellular dopamine release were also antagonized by mecamylamine. Galantamine attenuated the defect of the novelty-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). The ameliorating effect of galantamine on recognition memory in Meth-treated mice was negated by microinjection of an ERK inhibitor, PD98059, into the PFC. These results suggest that the ameliorating effect of galantamine on Meth-induced memory impairment is associated with indirect activation of dopamine D(1) receptor-ERK1/2 following augmentation with dopaminergic neurotransmission in the PFC through the allosteric activation of nAChRs. Galantamine could be a useful therapeutic agent for treating cognitive deficits in schizophrenia/Meth psychosis, as well as Alzheimer's disease.

引用

页码：1343 / 1354

页数：12

共 29 条

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