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The antipsychotic-like effects in rodents of YQA31 involve dopamine D3 and 5-HT1A receptor
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نویسنده
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gou h.-y. ,sun x. ,li f. ,wang z.-y. ,wu n. ,su r.-b. ,cong b. ,li j.
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منبع
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pharmacological reports - 2017 - دوره : 69 - شماره : 6 - صفحه:1125 -1130
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چکیده
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Background we previously reported that yqa31 is a dopamine d3 receptor antagonist with modest 5-ht1a receptor affinity and that it exhibits antipsychotic properties in animal models of schizophrenia. however,the contributions of d3 and 5-ht1a receptors in the anti-psychotic effects of yqa31 are not clear. the current study evaluated the role of these two receptors in the effect of yqa31 on the hyperactivity and novel object recognition deficit in mice. methods we used dopamine d3 receptor knockout mice and 5-ht1a receptor antagonist way100635 pretreatment,respectively,to investigate the involvement of these receptors in the effects of yqa31. the anti-psychotic effects were tested by inducing hyperlocomotion with methamphetamine or mk-801 and by inducing novel object recognition deficit with mk-801,which are the animal models to represent a positive symptom and a cognitive disorder. results yqa31 significantly inhibited mk-801-induced hyperlocomotion and novel object recognition deficit in wt mice,which was significantly inhibited by dopamine d3 receptor knockout. the 5-ht1a receptor antagonist,way100635,also blocked the effect of yqa31 in mk-801-induced novel object recognition deficit but not hyperlocomotion. the effect of yqa31 on methamphetamine-induced hyperlocomotion was not reversed by either dopamine d3 receptor knockout or way100635 pretreatment. conclusions these results demonstrate the different roles of dopamine d3 and 5-ht1a receptors in the anti-psychotic effects of yqa31. both dopamine d3 and 5-ht1a receptors contributed to the effects of yqa31 on the inhibition of mk-801-induced novel object recognition deficit,and the dopamine d3 receptor mediated the inhibiting effect of yqa31 on hyperlocomotion induced by mk-801. © 2017
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کلیدواژه
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5-HT1A receptor; Dopamine D3 receptor; Hyperactivity; Novel object recognition; Schizophrenia
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آدرس
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state key laboratory of toxicology and medical countermeasures,beijing key laboratory of neuropsychopharmacology,beijing institute of pharmacology and toxicology,beijing,china,hebei key laboratory of forensic medicine,department of forensic medicine,hebei medical university,shijiazhuang, China, state key laboratory of toxicology and medical countermeasures,beijing key laboratory of neuropsychopharmacology,beijing institute of pharmacology and toxicology,beijing,china,shenyang north hospital,shenyang, China, state key laboratory of toxicology and medical countermeasures,beijing key laboratory of neuropsychopharmacology,beijing institute of pharmacology and toxicology,beijing, China, state key laboratory of toxicology and medical countermeasures,beijing key laboratory of neuropsychopharmacology,beijing institute of pharmacology and toxicology,beijing, China, state key laboratory of toxicology and medical countermeasures,beijing key laboratory of neuropsychopharmacology,beijing institute of pharmacology and toxicology,beijing, China, state key laboratory of toxicology and medical countermeasures,beijing key laboratory of neuropsychopharmacology,beijing institute of pharmacology and toxicology,beijing, China, hebei key laboratory of forensic medicine,department of forensic medicine,hebei medical university,shijiazhuang, China, state key laboratory of toxicology and medical countermeasures,beijing key laboratory of neuropsychopharmacology,beijing institute of pharmacology and toxicology,beijing, China
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