Chemogenetic Inhibition of Dopamine D1-expressing Neurons in the Dorsal Striatum does not alter Methamphetamine Intake in either Male or Female Long Evans Rats.
Chemogenetic Inhibition of Dopamine D1-expressing Neurons in the Dorsal Striatum does not alter Methamphetamine Intake in either Male or Female Long Evans Rats.
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DOI：
10.1016/j.neulet.2020.134987
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发表时间：
2020-06-11
影响因子：
2.5
通讯作者：
Cadet JL
中科院分区：
文献类型：
--
作者：
Job MO;Chojnacki MR;Daiwile AP;Cadet JL
甲基苯丙胺（METH）使用障碍的生物化学和分子底物仍有待阐明。在啮齿类动物中，METH摄入量增加与背侧纹状体多巴胺D1受体（D1 R）表达增加相关。本研究评估了抑制纹状体D1 R表达对大鼠METH自我给药（SA）的潜在影响。我们显微注射Cre激活的腺相关病毒，将抑制性DREADD构建体hM 4D（Gi）-mCherry递送到雄性和雌性转基因Long Evans大鼠（Drd 1a-iCre #3）背侧纹状体中表达Cre重组酶的神经元（D1表达神经元）中。两周后，我们训练大鼠自我管理METH。一旦获得这种行为，在每次METH SA治疗前向大鼠腹膜内注射氯氮平-N-氧化物（CNO）或其载体（无菌水），以确定DREADD介导的抑制对METH摄入的影响。实验结束后，进行组织学检查以确认DREADD递送到背侧纹状体中。抑制性DREADD对雄性或雌性大鼠的METH SA无显著影响。死后组织学评估显示DREADD表达在背侧纹状体。我们的研究结果表明，抑制D1 R在背侧纹状体不抑制METH SA。它仍然有待确定，如果激活D1 R表达神经元可能有不同的行为影响。未来的研究还将评估影响其他大脑区域的D1 R活性是否会影响METH SA。
The biochemical and molecular substrates of methamphetamine (METH) use disorder remain to be elucidated. In rodents, increased METH intake is associated with increased expression of dopamine D1 receptors (D1R) in the dorsal striatum. The present study assessed potential effects of inhibiting striatal D1R expression on METH self-administration (SA) by rats. We microinjected Cre-activated adeno-associated viruses to deliver the inhibitory DREADD construct, hM4D (Gi) –mCherry, into neurons that expressed Cre-recombinase (D1-expressing neurons) in the dorsal striatum of male and female transgenic Long Evans rats (Drd1a-iCre#3). Two weeks later, we trained rats to self-administer METH. Once this behavior was acquired, intraperitoneal injections of clozapine-N-Oxide (CNO) or its vehicle (sterile water) were given to rats before each METH SA session to determine the effect of DREADD-mediated inhibition on METH intake. After the end of the experiments, histology was performed to confirm DREADD delivery into the dorsal striatum. There were no significant effects of the inhibitory DREADD on METH SA by male or female rats. Post-mortem histological assessment revealed DREADD expression in the dorsal striatum. Our results suggest that inhibition of D1R in the dorsal striatum does not suppress METH SA. It remains to be determined if activating D1R-expressing neurons might have differential behavioral effects. Future studies will also assess if impacting D1R activity in other brain regions might influence METH SA.
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影响因子：
3.3
作者：
CARBONI, E;IMPERATO, A;DICHIARA, G
通讯作者：
DICHIARA, G
影响因子：
3.4
作者：
Pena-Bravo, Jose Ignacio;Penrod, Rachel;Lavin, Antonieta
通讯作者：
Lavin, Antonieta
影响因子：
3.3
作者：
Bari, AA;Pierce, RC
通讯作者：
Pierce, RC
DOI：
10.1124/jpet.110.176610
发表时间：
2011-03-01
影响因子：
3.5
作者：
Frankel, Paul S.;Hoonakker, Amanda J.;Hanson, Glen R.
通讯作者：
Hanson, Glen R.
影响因子：
2.9
作者：
MCGREGOR, A;ROBERTS, DCS
通讯作者：
ROBERTS, DCS