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Post‐transcriptional regulation of dopamine D1 receptor expression in caudate‐putamen of cocaine‐sensitized mice
Author(s) -
Tobón Krishna E.,
Catuzzi Jennifer E.,
Cote Samantha R.,
Sonaike Adenike,
Kuzhikandathil Eldo V.
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12933
Subject(s) - dopamine receptor d1 , receptor , dopamine , dopamine receptor , dopamine receptor d2 , putamen , biology , messenger rna , medicine , endocrinology , chemistry , gene , biochemistry
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 have 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 m RNA , the expression of D1 receptor protein is not elevated. We determined that the post‐transcriptional regulation of D1 receptor m RNA is rapidly attenuated and D1 receptor protein levels increase within 30 min 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 with the levels of micro RNA 142‐3p and 382, both of which regulate D1 receptor protein expression. The levels of these two micro RNA s decreased significantly within 5 min 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 suggest a potential novel role for inherently labile micro RNA s in regulating the rapid expression of D1 receptor protein in cocaine‐sensitized animals.