Dopamine D 4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia
Several atypical antipsychotic drugs (APDs) have high affinity for the dopamine (DA) D receptor, but the relevance to the efficacy for the treatment of cognitive impairment associated with schizophrenia (CIAS) is poorly understood. The aim of this study was to investigate the effects of D receptor s...
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| Veröffentlicht in: | Journal of psychopharmacology (Oxford) 2017-04, Vol.31 (4), p.442-452 |
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| creator | Miyauchi, Masanori Neugebauer, Nichole M Meltzer, Herbert Y |
| description | Several atypical antipsychotic drugs (APDs) have high affinity for the dopamine (DA) D
receptor, but the relevance to the efficacy for the treatment of cognitive impairment associated with schizophrenia (CIAS) is poorly understood. The aim of this study was to investigate the effects of D
receptor stimulation or blockade on novel object recognition (NOR) in normal rats and on the sub-chronic phencyclidine (PCP)-induced novel object recognition deficit. The effect of the D
agonist, PD168077, and the D
antagonist, L-745,870, were studied alone, and in combination with clozapine and lurasidone. In normal rats, L-745,870 impaired novel object recognition, whereas PD168077 had no effect. PD168077 acutely reversed the sub-chronic phencyclidine-induced novel object recognition deficit. Co-administration of a sub-effective dose (SED) of PD168077 with a sub-effective dose of lurasidone also reversed this deficit, but a sub-effective dose of PD168077 with a sub-effective dose of clozapine, a more potent D
antagonist than lurasidone, did not reverse the sub-chronic phencyclidine-induced novel object recognition deficit. At a dose that did not induce a novel object recognition deficit, L-745,870 blocked the ability of clozapine, but not lurasidone, to reverse the novel object recognition deficit. D
receptor agonism has a beneficial effect on novel object recognition in sub-chronic PCP-treated rats and augments the cognitive enhancing efficacy of an atypical antipsychotic drug that lacks affinity for the D
receptor, lurasidone. |
| doi_str_mv | 10.1177/0269881117693746 |
| format | Article |
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receptor, but the relevance to the efficacy for the treatment of cognitive impairment associated with schizophrenia (CIAS) is poorly understood. The aim of this study was to investigate the effects of D
receptor stimulation or blockade on novel object recognition (NOR) in normal rats and on the sub-chronic phencyclidine (PCP)-induced novel object recognition deficit. The effect of the D
agonist, PD168077, and the D
antagonist, L-745,870, were studied alone, and in combination with clozapine and lurasidone. In normal rats, L-745,870 impaired novel object recognition, whereas PD168077 had no effect. PD168077 acutely reversed the sub-chronic phencyclidine-induced novel object recognition deficit. Co-administration of a sub-effective dose (SED) of PD168077 with a sub-effective dose of lurasidone also reversed this deficit, but a sub-effective dose of PD168077 with a sub-effective dose of clozapine, a more potent D
antagonist than lurasidone, did not reverse the sub-chronic phencyclidine-induced novel object recognition deficit. At a dose that did not induce a novel object recognition deficit, L-745,870 blocked the ability of clozapine, but not lurasidone, to reverse the novel object recognition deficit. D
receptor agonism has a beneficial effect on novel object recognition in sub-chronic PCP-treated rats and augments the cognitive enhancing efficacy of an atypical antipsychotic drug that lacks affinity for the D
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receptor, but the relevance to the efficacy for the treatment of cognitive impairment associated with schizophrenia (CIAS) is poorly understood. The aim of this study was to investigate the effects of D
receptor stimulation or blockade on novel object recognition (NOR) in normal rats and on the sub-chronic phencyclidine (PCP)-induced novel object recognition deficit. The effect of the D
agonist, PD168077, and the D
antagonist, L-745,870, were studied alone, and in combination with clozapine and lurasidone. In normal rats, L-745,870 impaired novel object recognition, whereas PD168077 had no effect. PD168077 acutely reversed the sub-chronic phencyclidine-induced novel object recognition deficit. Co-administration of a sub-effective dose (SED) of PD168077 with a sub-effective dose of lurasidone also reversed this deficit, but a sub-effective dose of PD168077 with a sub-effective dose of clozapine, a more potent D
antagonist than lurasidone, did not reverse the sub-chronic phencyclidine-induced novel object recognition deficit. At a dose that did not induce a novel object recognition deficit, L-745,870 blocked the ability of clozapine, but not lurasidone, to reverse the novel object recognition deficit. D
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receptor, lurasidone.</description><subject>Animals</subject><subject>Antipsychotic Agents - pharmacology</subject><subject>Benzamides - pharmacology</subject><subject>Clozapine - pharmacology</subject><subject>Cognitive Dysfunction - drug therapy</subject><subject>Cognitive Dysfunction - metabolism</subject><subject>Female</subject><subject>Lurasidone Hydrochloride - pharmacology</subject><subject>Phencyclidine - pharmacology</subject><subject>Piperazines - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Pyrroles - pharmacology</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Receptor, Serotonin, 5-HT1A - metabolism</subject><subject>Receptors, Dopamine D4 - metabolism</subject><subject>Schizophrenia - drug therapy</subject><subject>Schizophrenia - metabolism</subject><subject>Serotonin 5-HT1 Receptor Agonists - pharmacology</subject><issn>0269-8811</issn><issn>1461-7285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1LAzEQhoMotlbvniR_YDXJZpONN2n9goIgel6y6axN2U2WJFtQ8L_bpdWDpxnmfZ85PAhdUnJNqZQ3hAlVlnS3C5VLLo7QlHJBM8nK4hhNxzgb8wk6i3FDCBVcFKdowsqcSyboFH0vfK876wAvMMcBDPTJBxyT7YZWJ-sdNt6lYOshQcTJY-e30GJfb8CkEfAfzo69W_wKLWy1MzDWDvctYNv12oYOXMLW4WjW9sv36wDO6nN00ug2wsVhztD7w_3b_Clbvjw-z--WmaFKpIzWyrCVlqKWihVQ5yvVGEpKYMBowRstNCdGUVVwokxJBM9Zo2u5KxhOtMhniOz_muBjDNBUfbCdDp8VJdVosvpvcodc7ZF-qDtY_QG_6vIfzoxw1g</recordid><startdate>201704</startdate><enddate>201704</enddate><creator>Miyauchi, Masanori</creator><creator>Neugebauer, Nichole M</creator><creator>Meltzer, Herbert Y</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201704</creationdate><title>Dopamine D 4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia</title><author>Miyauchi, Masanori ; Neugebauer, Nichole M ; Meltzer, Herbert Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c196t-1b9c2da76b7925eb3d9fc108e2e2154fa6a40c9195409c806432fab78e2c40a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antipsychotic Agents - pharmacology</topic><topic>Benzamides - pharmacology</topic><topic>Clozapine - pharmacology</topic><topic>Cognitive Dysfunction - drug therapy</topic><topic>Cognitive Dysfunction - metabolism</topic><topic>Female</topic><topic>Lurasidone Hydrochloride - pharmacology</topic><topic>Phencyclidine - pharmacology</topic><topic>Piperazines - pharmacology</topic><topic>Pyridines - pharmacology</topic><topic>Pyrroles - pharmacology</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Receptor, Serotonin, 5-HT1A - metabolism</topic><topic>Receptors, Dopamine D4 - metabolism</topic><topic>Schizophrenia - drug therapy</topic><topic>Schizophrenia - metabolism</topic><topic>Serotonin 5-HT1 Receptor Agonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyauchi, Masanori</creatorcontrib><creatorcontrib>Neugebauer, Nichole M</creatorcontrib><creatorcontrib>Meltzer, Herbert Y</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of psychopharmacology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyauchi, Masanori</au><au>Neugebauer, Nichole M</au><au>Meltzer, Herbert Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dopamine D 4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia</atitle><jtitle>Journal of psychopharmacology (Oxford)</jtitle><addtitle>J Psychopharmacol</addtitle><date>2017-04</date><risdate>2017</risdate><volume>31</volume><issue>4</issue><spage>442</spage><epage>452</epage><pages>442-452</pages><issn>0269-8811</issn><eissn>1461-7285</eissn><abstract>Several atypical antipsychotic drugs (APDs) have high affinity for the dopamine (DA) D
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receptor stimulation or blockade on novel object recognition (NOR) in normal rats and on the sub-chronic phencyclidine (PCP)-induced novel object recognition deficit. The effect of the D
agonist, PD168077, and the D
antagonist, L-745,870, were studied alone, and in combination with clozapine and lurasidone. In normal rats, L-745,870 impaired novel object recognition, whereas PD168077 had no effect. PD168077 acutely reversed the sub-chronic phencyclidine-induced novel object recognition deficit. Co-administration of a sub-effective dose (SED) of PD168077 with a sub-effective dose of lurasidone also reversed this deficit, but a sub-effective dose of PD168077 with a sub-effective dose of clozapine, a more potent D
antagonist than lurasidone, did not reverse the sub-chronic phencyclidine-induced novel object recognition deficit. At a dose that did not induce a novel object recognition deficit, L-745,870 blocked the ability of clozapine, but not lurasidone, to reverse the novel object recognition deficit. D
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| subjects | Animals Antipsychotic Agents - pharmacology Benzamides - pharmacology Clozapine - pharmacology Cognitive Dysfunction - drug therapy Cognitive Dysfunction - metabolism Female Lurasidone Hydrochloride - pharmacology Phencyclidine - pharmacology Piperazines - pharmacology Pyridines - pharmacology Pyrroles - pharmacology Rats Rats, Long-Evans Receptor, Serotonin, 5-HT1A - metabolism Receptors, Dopamine D4 - metabolism Schizophrenia - drug therapy Schizophrenia - metabolism Serotonin 5-HT1 Receptor Agonists - pharmacology |
| title | Dopamine D 4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia |
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