Department of Psychological and Brain Sciences, Behavioral and Cellular Neuroscience, Interdisciplinary Program in Neuroscience, Texas A&M Institute for Neuroscience (TAMIN), Texas A&M University, 4235 TAMU, College Station, TX 77843, USA.
Department of Psychological and Brain Sciences, Behavioral and Cellular Neuroscience, Interdisciplinary Program in Neuroscience, Texas A&M Institute for Neuroscience (TAMIN), Texas A&M University, 4235 TAMU, College Station, TX 77843, USA.
Drug Alcohol Depend. 2018 Jul 1;188:113-118. doi: 10.1016/j.drugalcdep.2018.03.021. Epub 2018 Apr 22.
The association with opioid-abusing individuals or even the perception of opioid abuse by peers are risk factors for the initiation and escalation of abuse. Similarly, we demonstrated that morphine-treated animals housed with only morphine-treated animals (referred to as morphine only) acquire morphine conditioned place-preference (CPP) more readily than morphine-treated animals housed with drug-naïve animals (referred to as morphine cage-mates). However, the molecular mechanisms underlying these effects are still elusive.
Mice received repeated morphine or saline while housed as saline only, morphine only, or cage-mates. Then, they were examined for the expression levels of D1 dopamine receptor (D1DR), D2 dopamine receptor (D2DR), dopamine transporter (DAT), oxytocin, and Arginine-vasopressin (AVP) in the striatum using qPCR. Additionally, we examined the effects of the AVP-V1b receptor antagonist, SSR149415, on the acquisition of morphine conditioned place-preference (CPP).
Increased striatal expression of D1DR and AVP was observed in morphine only animals, but not morphine cage-mates. No significant effects were observed on the striatal expression of D2DR, DAT, or oxytocin. Antagonizing the AVP-V1b receptors decreased the acquisition of morphine CPP in the morphine only mice, but did not alter the acquisition of morphine CPP in the morphine cage-mate mice.
Housing with drug-naïve animals protects against the increase in striatal expression of D1DR and AVP elicited by morphine exposure. Moreover, our studies suggest that the protective effect of housing with drug-naïve animals on the acquisition of morphine reward might be, at least partially, mediated by AVP.
与阿片类药物滥用者交往，甚至被同伴认为有阿片类药物滥用行为，都是开始和加重滥用的风险因素。同样，我们发现，与仅接受吗啡处理的动物（称为吗啡单养）相比，与仅接受吗啡处理的动物（称为吗啡单养）一起饲养的接受吗啡处理的动物（称为吗啡笼伴）更容易获得吗啡条件性位置偏好（CPP）。然而，这些影响的分子机制仍不清楚。
将小鼠接受重复吗啡或生理盐水处理，同时分别单独饲养于生理盐水组、吗啡单养组或笼伴组。然后，使用 qPCR 检测纹状体中 D1 多巴胺受体（D1DR）、D2 多巴胺受体（D2DR）、多巴胺转运蛋白（DAT）、催产素和精氨酸加压素（AVP）的表达水平。此外，我们还研究了 AVP-V1b 受体拮抗剂 SSR149415 对吗啡条件性位置偏好（CPP）获得的影响。
仅在吗啡单养组中观察到纹状体中 D1DR 和 AVP 的表达增加，而在吗啡笼伴组中没有观察到。在纹状体中 D2DR、DAT 或催产素的表达没有观察到显著影响。拮抗 AVP-V1b 受体可降低吗啡单养组中吗啡 CPP 的获得，但不改变吗啡笼伴组中吗啡 CPP 的获得。
与未用药的动物一起饲养可防止因暴露于吗啡而引起的纹状体中 D1DR 和 AVP 表达的增加。此外，我们的研究表明，与未用药的动物一起饲养对获得吗啡奖赏的保护作用可能至少部分是由 AVP 介导的。
