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

Yukihiro Noda, Akihiro Mouri, Yu Ando, Yukari Waki, Shin Nosuke Yamada, Akira Yoshimi, Kiyofumi Yamada, Norio Ozaki, Dayong Wang, Toshitaka Nabeshima

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Abstract 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 D1 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 D1 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.

Original languageEnglish
Pages (from-to)1343-1354
Number of pages12
JournalInternational Journal of Neuropsychopharmacology
Volume13
Issue number10
DOIs
Publication statusPublished - 01-11-2010
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this