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Synergistic effect of combined treatment with risperidone and galantamine on phencyclidine-induced impairment of latent visuospatial learning and memory: Role of nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission.
Neuropharmacology. 2007 Sep; 53(3):379-89.N

Abstract

The clinically achievable efficacy of the atypical antipsychotics on cognitive symptoms of schizophrenia is practically limited by their dose-dependent side effects. Thus, there is the need for adjuvant treatments or strategies for the cognitive impairments. Further, human autopsy and genetic data in schizophrenia have indicated the existence of the abnormality of nicotinic acetylcholine receptors (nAChR). In the present study, we aimed to investigate the synergistic effect and mechanisms of a combined treatment with an atypical antipsychotic risperidone and galantamine, which is a nAChR-allosteric modulator and a modest cholinesterase inhibitor, on the impairment of latent visuospatial learning and memory in mice resembling the cognitive impairment of schizophrenia. Repeated treatment with phencyclidine (PCP, 10 mg/kg, 14 days)-induced cognitive impairment in mice in a one trial water-finding test was used as a model of the cognitive impairment of schizophrenia. In vivo microdialysis was used to investigate the extracellular concentration of dopamine in the medial prefrontal cortex (mPFC). Combined treatment with galantamine and risperidone, at low, ineffective doses (both at 0.05 mg/kg) showed a synergistic effect to reverse cognitive impairment and increase extracellular concentration of dopamine in the mPFC. The synergistic behavioral effect was abolished by a dopamine-D1 receptor antagonist, SCH 23390, and a nAChR antagonist, mecamylamine, but not a muscarinic AChR (mAChR) antagonist, scopolamine. Mecamylamine also blocked the synergistic effect on dopamine release in the mPFC of PCP-treated mice. The study indicates that galantamine and risperidone may have synergistic effect on the cognitive impairments in schizophrenia patients by synergistically promoting the nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission.

Authors+Show Affiliations

Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, 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

17632185

Citation

Wang, Dayong, et al. "Synergistic Effect of Combined Treatment With Risperidone and Galantamine On Phencyclidine-induced Impairment of Latent Visuospatial Learning and Memory: Role of nAChR Activation-dependent Increase of Dopamine D1 Receptor-mediated Neurotransmission." Neuropharmacology, vol. 53, no. 3, 2007, pp. 379-89.
Wang D, Noda Y, Zhou Y, et al. Synergistic effect of combined treatment with risperidone and galantamine on phencyclidine-induced impairment of latent visuospatial learning and memory: Role of nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission. Neuropharmacology. 2007;53(3):379-89.
Wang, D., Noda, Y., Zhou, Y., Nitta, A., Furukawa, H., & Nabeshima, T. (2007). Synergistic effect of combined treatment with risperidone and galantamine on phencyclidine-induced impairment of latent visuospatial learning and memory: Role of nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission. Neuropharmacology, 53(3), 379-89.
Wang D, et al. Synergistic Effect of Combined Treatment With Risperidone and Galantamine On Phencyclidine-induced Impairment of Latent Visuospatial Learning and Memory: Role of nAChR Activation-dependent Increase of Dopamine D1 Receptor-mediated Neurotransmission. Neuropharmacology. 2007;53(3):379-89. PubMed PMID: 17632185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic effect of combined treatment with risperidone and galantamine on phencyclidine-induced impairment of latent visuospatial learning and memory: Role of nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission. AU - Wang,Dayong, AU - Noda,Yukihiro, AU - Zhou,Yuan, AU - Nitta,Atsumi, AU - Furukawa,Hiroshi, AU - Nabeshima,Toshitaka, Y1 - 2007/06/12/ PY - 2007/03/22/received PY - 2007/05/02/revised PY - 2007/05/25/accepted PY - 2007/7/17/pubmed PY - 2007/12/7/medline PY - 2007/7/17/entrez SP - 379 EP - 89 JF - Neuropharmacology JO - Neuropharmacology VL - 53 IS - 3 N2 - The clinically achievable efficacy of the atypical antipsychotics on cognitive symptoms of schizophrenia is practically limited by their dose-dependent side effects. Thus, there is the need for adjuvant treatments or strategies for the cognitive impairments. Further, human autopsy and genetic data in schizophrenia have indicated the existence of the abnormality of nicotinic acetylcholine receptors (nAChR). In the present study, we aimed to investigate the synergistic effect and mechanisms of a combined treatment with an atypical antipsychotic risperidone and galantamine, which is a nAChR-allosteric modulator and a modest cholinesterase inhibitor, on the impairment of latent visuospatial learning and memory in mice resembling the cognitive impairment of schizophrenia. Repeated treatment with phencyclidine (PCP, 10 mg/kg, 14 days)-induced cognitive impairment in mice in a one trial water-finding test was used as a model of the cognitive impairment of schizophrenia. In vivo microdialysis was used to investigate the extracellular concentration of dopamine in the medial prefrontal cortex (mPFC). Combined treatment with galantamine and risperidone, at low, ineffective doses (both at 0.05 mg/kg) showed a synergistic effect to reverse cognitive impairment and increase extracellular concentration of dopamine in the mPFC. The synergistic behavioral effect was abolished by a dopamine-D1 receptor antagonist, SCH 23390, and a nAChR antagonist, mecamylamine, but not a muscarinic AChR (mAChR) antagonist, scopolamine. Mecamylamine also blocked the synergistic effect on dopamine release in the mPFC of PCP-treated mice. The study indicates that galantamine and risperidone may have synergistic effect on the cognitive impairments in schizophrenia patients by synergistically promoting the nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17632185/Synergistic_effect_of_combined_treatment_with_risperidone_and_galantamine_on_phencyclidine_induced_impairment_of_latent_visuospatial_learning_and_memory:_Role_of_nAChR_activation_dependent_increase_of_dopamine_D1_receptor_mediated_neurotransmission_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(07)00162-1 DB - PRIME DP - Unbound Medicine ER -