Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model

Dayong Wang, Yukihiro Noda, Yuan Zhou, Atsumi Nitta, Hiroshi Furukawa, Toshitaka Nabeshima

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Social withdrawal is the first sign and key component of the negative symptoms of schizophrenia. The efficacy of risperidone, an atypical antipsychotic, on the symptom is practically limited by dose-dependent side effects in clinical trials, therefore there is the need for adjuvant treatments. In the present study, we aimed to investigate the synergistic effect and mechanism of risperidone and galantamine, which is a nicotinic acetylcholine receptor (nAChR)-allosteric modulator and a modest cholinesterase inhibitor, on phencyclidine (PCP)-treated mouse model of social withdrawal. At non-effective doses by themselves, co-administration of galantamine (0.05 mg/kg) and risperidone (0.05 mg/kg) showed synergistic effects on PCP-induced impairments of social interaction and dopamine release in the medial prefrontal cortex (mPFC). The behavioral synergistic effect was abolished by the administration of a dopamine-D1 receptor antagonist, SCH 23390 (0.02 mg/kg, systemic; or 0.02 μg/0.5 μL/mouse, intra-mPFC), and a nAChR antagonist, mecamylamine (3 mg/kg), but not a muscarinic receptor antagonist, scopolamine (0.1 mg/kg). Mecamylamine (3 mg/kg) also abolished the synergistic effect on dopamine release in the mPFC. We conclude that galantamine may have synergistic effect with risperidone on the negative symptom of social withdrawal in schizophrenia, which is mediated by dopamine-D1 receptors in the mPFC through nAChR activation-increased dopamine release.

Original languageEnglish
Pages (from-to)1179-1187
Number of pages9
JournalNeuropharmacology
Volume52
Issue number4
DOIs
Publication statusPublished - 01-03-2007
Externally publishedYes

Fingerprint

Galantamine
Phencyclidine
Risperidone
Interpersonal Relations
Prefrontal Cortex
Nicotinic Receptors
Animal Models
Mecamylamine
Dopamine D1 Receptors
Dopamine
Schizophrenia
Substance Withdrawal Syndrome
Muscarinic Antagonists
Scopolamine Hydrobromide
Dopamine Antagonists
Cholinesterase Inhibitors
Cholinergic Antagonists
Muscarinic Receptors
Antipsychotic Agents
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Wang, Dayong ; Noda, Yukihiro ; Zhou, Yuan ; Nitta, Atsumi ; Furukawa, Hiroshi ; Nabeshima, Toshitaka. / Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model. In: Neuropharmacology. 2007 ; Vol. 52, No. 4. pp. 1179-1187.
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Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model. / Wang, Dayong; Noda, Yukihiro; Zhou, Yuan; Nitta, Atsumi; Furukawa, Hiroshi; Nabeshima, Toshitaka.

In: Neuropharmacology, Vol. 52, No. 4, 01.03.2007, p. 1179-1187.

Research output: Contribution to journalArticle

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