TY - JOUR
T1 - Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model
AU - Wang, Dayong
AU - Noda, Yukihiro
AU - Zhou, Yuan
AU - Nitta, Atsumi
AU - Furukawa, Hiroshi
AU - Nabeshima, Toshitaka
N1 - Funding Information:
We appreciate Janssen Pharmaceutical K.K. for providing purified galantamine and risperidone. This work was supported, in part, by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (14370031) (15922139) (16922036) (17390018), by a Grant-in-aid for Scientific Research on Priority Areas on “Elucidation of glia-neuron network-mediated information processing systems” from the Ministry of Education, Culture, Sports, Science and Technology (16047214), by Funds from Integrated Molecular Medicine for Neuronal and Neoplastic Disorders (21st Century COE program), by the Japan Brain Foundation, by the Mitsubishi Pharma Research Foundation, by an SRF Grant for Biomedical Research, and by Brain Research Center of the 21st Century Frontier Research Program of the Ministry of Science and Technology, Republic of Korea.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Galantamine
KW - Risperidone
KW - Schizophrenia
KW - Social withdrawal
KW - Synergistic effects
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U2 - 10.1016/j.neuropharm.2006.12.007
DO - 10.1016/j.neuropharm.2006.12.007
M3 - Article
C2 - 17313962
AN - SCOPUS:33847271559
SN - 0028-3908
VL - 52
SP - 1179
EP - 1187
JO - Neuropharmacology
JF - Neuropharmacology
IS - 4
ER -