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Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model.
Neuropharmacology. 2007 Mar; 52(4):1179-87.N

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 (0.05mg/kg) and risperidone (0.05mg/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-D(1) receptor antagonist, SCH 23390 (0.02mg/kg, systemic; or 0.02microg/0.5microL/mouse, intra-mPFC), and a nAChR antagonist, mecamylamine (3mg/kg), but not a muscarinic receptor antagonist, scopolamine (0.1mg/kg). Mecamylamine (3mg/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-D(1) receptors in the mPFC through nAChR activation-increased dopamine release.

Authors+Show Affiliations

Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; Japanese Society of Pharmacopoeia, Tokyo 150-0002, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17313962

Citation

Wang, Dayong, et al. "Synergistic Effect of Galantamine With Risperidone On Impairment of Social Interaction in Phencyclidine-treated Mice as a Schizophrenic Animal Model." Neuropharmacology, vol. 52, no. 4, 2007, pp. 1179-87.
Wang D, Noda Y, Zhou Y, et al. Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model. Neuropharmacology. 2007;52(4):1179-87.
Wang, D., Noda, Y., Zhou, Y., Nitta, A., Furukawa, H., & Nabeshima, T. (2007). Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model. Neuropharmacology, 52(4), 1179-87.
Wang D, et al. Synergistic Effect of Galantamine With Risperidone On Impairment of Social Interaction in Phencyclidine-treated Mice as a Schizophrenic Animal Model. Neuropharmacology. 2007;52(4):1179-87. PubMed PMID: 17313962.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2007/01/14/ PY - 2006/10/23/received PY - 2006/12/08/revised PY - 2006/12/21/accepted PY - 2007/2/23/pubmed PY - 2007/6/2/medline PY - 2007/2/23/entrez SP - 1179 EP - 87 JF - Neuropharmacology JO - Neuropharmacology VL - 52 IS - 4 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 (0.05mg/kg) and risperidone (0.05mg/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-D(1) receptor antagonist, SCH 23390 (0.02mg/kg, systemic; or 0.02microg/0.5microL/mouse, intra-mPFC), and a nAChR antagonist, mecamylamine (3mg/kg), but not a muscarinic receptor antagonist, scopolamine (0.1mg/kg). Mecamylamine (3mg/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-D(1) receptors in the mPFC through nAChR activation-increased dopamine release. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17313962/Synergistic_effect_of_galantamine_with_risperidone_on_impairment_of_social_interaction_in_phencyclidine_treated_mice_as_a_schizophrenic_animal_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(07)00003-2 DB - PRIME DP - Unbound Medicine ER -