The above findings support a role for miRNAs in striatum in regulating drug reward, but which miRNAs are involved? Many laboratories have identified specific miRNAs whose expression is altered by exposure to drugs of abuse and that may play a role in regulating their motivational properties. Indeed, expression of various miRNAs is altered in the prefrontal cortex, striatum and other addiction-relevant brain sites in response to exposure to drugs of abuse. As detailed lists describing which miRNAs are altered in response to particular drugs are presented elsewhere, these effects won't be considered here.106-112 Instead, the impact of altering expression of specific miRNAs on the motivational properties of addictive drugs will be considered. Chandresekar and Dreyer have shown that the miRNAs, miRNA-124a and let-7d, were downregulated in striatum in response to cocaine treatment.113 Moreover, virus-mediated overexpression of these miRNAs in striatum decreased expression of BDNF and the dopamine D3 receptor, two key regulators of drug-seeking behaviors.113 This suggests that miRNA-124a and let-7d may regulate cocaine-induced remodeling of the striatum and thereby influence the motivational properties of the drug. Consistent with this
