A challenge for developing effective treatments for substance use disorders (SUDs) is understanding how environmental variables alter the efficacy of therapeutics. Environmental enrichment (EC) enhances brain development and protects against behaviors associated with drug abuse vulnerability when compared to rats reared in isolation (IC) or standard conditions (SC). EC rearing enhances the expression and function of metabotropic glutamate receptor_2/3 (mGlurR_2/3) and activating mGluR_2/3 reduces psychostimulant self-administration (SA). However, the ability for mGluR_2/3 activation to suppress amphetamine (AMP) SA in differentially reared rats is not determined. Therefore, we tested the hypothesis EC reduces AMP (SA) by augmenting mGluR_2/3 function. At postnatal day 21, male Sprague-Dawley rats were assigned to EC, IC, or SC environments for 30 days. Then, they acquired AMP SA and were moved to a progressive ratio (PR) schedule of reinforcement. EC, IC, and SC rats were pretreated with LY379268 (vehicle, 0.3 and 1 mg/kg), a selective mGluR_2/3 agonist, before PR behavioral sessions. Linear mixed effects analysis determined EC rats had reduced motivation for AMP SA when compared to IC or SC rats and that LY379268 dose-dependently suppressed AMP SA, but there was no evidence of an interaction. Cumming/Gardner-Altman estimation plots illustrate that the 0.3 mg/kg dose suppressed infusions in EC rats while the 1 mg/kg dose suppressed infusions in SC rats. LY379268 was incapable of suppressing the motivation for AMP SA in IC rats. Controlling for baseline differences in differentially reared rats remains a challenge. Normalizing to a baseline introduced error which is illustrated in the precision of the estimated effect size differences. The data indicate that environmental enrichment enhances the ability of a selective mGluR_2/3 agonist to suppress AMP SA and indicates the functional status of the mGluR_2/3 is formed during development. Therefore, environmental history must be considered when evaluating pharmacological therapeutics particularly those aimed at the mGluR_2/3.

开发针对物质使用障碍（SUD）的有效疗法的挑战是了解环境变量如何改变疗法的功效。与隔离（IC）或标准条件（SC）饲养的大鼠相比，环境富集（EC）可以增强大脑发育并防止与药物滥用脆弱性相关的行为。EC饲养提高了代谢型谷氨酸受体_2/3（mGlurR _2/3）的表达和功能，激活mGluR _2/3减少了精神兴奋剂的自我给药（SA）。但是，尚未确定mGluR _2/3激活抑制差异饲养大鼠的苯丙胺（AMP）SA的能力。因此，我们测试了假设EC通过增加mGluR降低AMP（SA）_2/3功能。出生后第21天，将雄性Sprague-Dawley大鼠分为EC，IC或SC环境30天。然后，他们获得了AMP SA，并被转移到逐步进行配筋的计划中。EC，IC和SC大鼠用LY379268（媒介物0.3和1 mg / kg），选择性mGluR _2/3预处理激动剂，在PR行为会议之前。线性混合效应分析确定，与IC或SC大鼠相比，EC大鼠的AMP SA动力降低，LY379268剂量依赖性抑制AMP SA，但没有相互作用的证据。Cumming / Gardner-Altman估计图显示，0.3 mg / kg剂量可抑制EC大鼠的输注，而1 mg / kg剂量可抑制SC大鼠的输注。LY379268无法抑制IC大鼠中AMP SA的动机。控制差异饲养大鼠的基线差异仍然是一个挑战。归一化为基线引入的误差，该误差以估计的效应大小差异的精度表示。数据表明环境富集增强了选择性mGluR _2/3的能力抑制AMP SA的激动剂，并表明在发育过程中形成了mGluR _2/3的功能状态。因此，在评估药理学疗法时，尤其是针对mGluR _2/3的药理疗法时，必须考虑环境史。