Post‐transcriptional regulation of dopamine D1 receptor expression in caudate‐putamen of cocaine‐sensitized mice

Abstract

The dopamine D1 receptor is centrally involved in mediating the effects of cocaine and is essential for cocaine-induced locomotor sensitization. Changes in D1 receptor expression has been reported in various models of cocaine addiction; however, the mechanisms that mediate these changes in D1 receptor expression are not well understood. Using preadolescent drd1a-EGFP mice and a binge cocaine treatment protocol we demonstrate that the D1 receptor is post-transcriptionally regulated in the caudate-putamen of cocaine-sensitized animal. While cocaine-sensitized mice express high levels of steady state D1 receptor mRNA, the expression of D1 receptor protein is not elevated. We determined that the post-transcriptional regulation of D1 receptor mRNA is rapidly attenuated and D1 receptor protein levels increase within thirty minutes when the sensitized mice are challenged with cocaine. The rapid increase in D1 receptor protein levels requires de novo protein synthesis and correlates with the cocaine-induced hyperlocomotor activity in the cocaine-sensitized mice. The increase in D1 receptor protein levels in the caudate-putamen inversely correlated to the levels of microRNA 142-3p and 382, both of which regulate D1 receptor protein expression. The levels of these two microRNAs decreased significantly within five minutes of cocaine challenge in sensitized mice. The results provide novel insights into the previously unknown rapid kinetics of D1 receptor protein expression which occurs in a time scale that is comparable to the expression of immediate early genes. Furthermore, the results suggests a potential novel role for inherently labile microRNAs in regulating the rapid expression of D1 receptor protein in cocaine-sensitized animals.

Cerebellum Transcriptome of Mice Bred for High Voluntary Activity Offers Insights into Locomotor Control and Reward-Dependent Behaviors

“…Dopamine receptor D1 (Drd1) was over-expressed in the cerebellum of H relative to C genotype mice. This result is consistent with the over-expression of Drd1 in the caudate-putamen of cocaine-sensitized mice relative to control [105] and reports that dopamine receptors D1 and D2 systems mediate the effects of cocaine on cerebellar neurons of adult rats [106]. Also, endogenous drug administration simulates D1 receptor, which leads to the expression of D2 receptor-mediated reward-driven behaviors and gene expression changes in non-cerebellar brain regions [105, 107–110].…”

“…This result is consistent with the over-expression of Drd1 in the caudate-putamen of cocaine-sensitized mice relative to control [105] and reports that dopamine receptors D1 and D2 systems mediate the effects of cocaine on cerebellar neurons of adult rats [106]. Also, endogenous drug administration simulates D1 receptor, which leads to the expression of D2 receptor-mediated reward-driven behaviors and gene expression changes in non-cerebellar brain regions [105, 107–110]. Both D1-like and D2-like dopamine receptors are involved in the response of rats who are taught to perform a behavior in order to receive pleasurable electrical stimulation [111, 112].…”

Early Life Stress and the Onset of Obesity: Proof of MicroRNAs’ Involvement Through Modulation of Serotonin and Dopamine Systems’ Homeostasis

“…Increased evidence points out that several components of the dopaminergic system are influenced by some miRNAs ( Table 2 ). DRD1 appears to be regulated by miR-504 ( Zhang et al, 2013 ), rno-miR-105 ( Zhao et al, 2017 ), and for the cluster of hsa-miR-15a-5p, hsa-miR-15b-5p, and hsa-miR-16-5p, and mmu-miR-142-3p ( Tobón et al, 2012 , 2015 ). The expression of the DRD2 is modified by miR-143-3p ( Wang et al, 2019 ), miR-200a ( Wu et al, 2018 ), miR-504 ( Zhang et al, 2013 ), hsa-miR-9, and hsa-miR-326 ( Shi et al, 2014 ; Zhang et al, 2015 ; Gangisetty et al, 2017 ; Mavrikaki et al, 2019 ).…”

The psychoactive cathinone derivative pyrovalerone alters locomotor activity and decreases dopamine receptor expression in zebrafish (Danio rerio)

“…Thus, there is evidence that DAT-acting drugs can regulate dopamine receptor expression. Conversely, the administration of cocaine has been shown to increase initial levels of D1 receptor proteins as reported by Tobón, Catuzzi, Cote, Sonaike, and Kuzhikandathil (2015). However, it is plausible that chronic exposure to amphetamines, and cathinones, could reduce D1 receptor expression after an acute increase in D1 proteins.…”