摘要
OBJECTIVE Glutamatergic projections from prefrontal cortex(PFc) to nucleus accumbens(NAc) regulate the dopamine(DA) release in NAc.However,it is not clear whether this circuit is effective for the reward and motivation of heroin addiction.Our study investigates the effects of metabotropic glutamate receptor 2/3(mGluR2/3) and the projections from ventromedial prefrontal cortex(vmPFc) to the NAc shell on the reward and motivation of heroin-addicted rats.METHODS First,rats were trained to selfadministration for 14 d.On the 15 thday,parts of rats were injected with mGluR 2/3 agonist LY379268(0.1,0.3 and 1.0 mg·kg-1,ip) systematically and another parts of rats were bilaterally microinjected with LY379268(0.3 and 1.0 g·L^(-1))at the volume of 0.5 μL into the ventral tegmental area(VTA),NAc core or NAc shell,respectively.All rats were followed by heroin self-administration testing under fixed ratio 1(FR1) schedule or progressed ratio(PR) schedule to observe the effect of LY379268 on the heroin reward or motivation.Second,rats were injected chemogenetic glutamatergic virus(pAAV-CaMKIIa-hM3 D(Gq)-mCherry or pAOV-CaMKIIa-hM4 D(Gi)-mCherry-3 Flag) or negative control virus in vmPFc,and trained to heroin self-administration for 14 d.On the 15 thday,rats were bilateral y microinjected with clozapine-N-oxide(CNO,1 mmol·L^(-1),0.5 μL) into NAc shell and tested the effect on the heroin reward or motivation.Finally,rats were injected optogenetical glutamatergic virus(AAV2/9-CaM KⅡ-hChR2-EYFP) or negative control virus in vmPFc,implanted 16 channel photoelectrode in ipsilateral NAc shell,and trained to heroin selfadministration for 14 d.On the 15 thday,rats were tested heroin reward under FR1 procedure with blue light stimulation in the wavelength of470 nm,frequency of 25 HZ and power of 5 mW.Each stimulation lasting for 1 h and interval for1 h.The spike changes before and after stimulation in NAc Shel neural nerve was recorded.RESULTS LY379268 cloud dose-dependent attenuated the heroin reward or motivation and the local ef
OBJECTIVE Glutamatergic projections from prefrontal cortex(PFc) to nucleus accumbens(NAc) regulate the dopamine(DA) release in NAc.However,it is not clear whether this circuit is effective for the reward and motivation of heroin addiction.Our study investigates the effects of metabotropic glutamate receptor 2/3(mGluR2/3) and the projections from ventromedial prefrontal cortex(vmPFc) to the NAc shell on the reward and motivation of heroin-addicted rats.METHODS First,rats were trained to selfadministration for 14 d.On the 15 thday,parts of rats were injected with mGluR 2/3 agonist LY379268(0.1,0.3 and 1.0 mg·kg-1,ip) systematically and another parts of rats were bilaterally microinjected with LY379268(0.3 and 1.0 g·L^(-1))at the volume of 0.5 μL into the ventral tegmental area(VTA),NAc core or NAc shell,respectively.All rats were followed by heroin self-administration testing under fixed ratio 1(FR1) schedule or progressed ratio(PR) schedule to observe the effect of LY379268 on the heroin reward or motivation.Second,rats were injected chemogenetic glutamatergic virus(pAAV-CaMKIIa-hM3 D(Gq)-mCherry or pAOV-CaMKIIa-hM4 D(Gi)-mCherry-3 Flag) or negative control virus in vmPFc,and trained to heroin self-administration for 14 d.On the 15 thday,rats were bilateral y microinjected with clozapine-N-oxide(CNO,1 mmol·L^(-1),0.5 μL) into NAc shell and tested the effect on the heroin reward or motivation.Finally,rats were injected optogenetical glutamatergic virus(AAV2/9-CaM KⅡ-hChR2-EYFP) or negative control virus in vmPFc,implanted 16 channel photoelectrode in ipsilateral NAc shell,and trained to heroin selfadministration for 14 d.On the 15 thday,rats were tested heroin reward under FR1 procedure with blue light stimulation in the wavelength of470 nm,frequency of 25 HZ and power of 5 mW.Each stimulation lasting for 1 h and interval for1 h.The spike changes before and after stimulation in NAc Shel neural nerve was recorded.RESULTS LY379268 cloud dose-dependent attenuated the heroin reward or motivation and the local ef
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2018年第9期725-726,共2页
Chinese Journal of Pharmacology and Toxicology
基金
National Basic Research Program of China(2015CB553504)
National Natural Science Foundationof China (81471350
81671321)
Natural Science Foundation of Ningbo Municipality,Zhejiang Province, China (2017A610214).
