Influence of delta opioid receptors in differentiation and protection of dopaminergic neurons

Current studies were iniciated to address whether morphine would exert its action as a neuroprotector through the delta opioid receptors from zebrafish by regulating the expression of miR‐133b. By silencing each delta opioid receptor duplicate from zebrafish, ZfDOR1 and ZfDOR2, we show that although some changes can be observed regarding the expression of miR‐133b and its targets, morphine is able to modulate these changes. However, the changes induced by the simultaneous knock‐down of ZfDOR1 and ZfDOR2 on the expression of the dopaminergic‐related genes are not altered by exposure to morphine. We demonstrate as well that these receptors protect dopaminergic neurons against glutamate damage, and in their absence, morphine is not able to inhibit this effect. Our results show that both delta opioid receptors from zebrafish are needed in the differentiation of the dopaminergic system. Our study suggests that the delta opioid receptors increase the addictive properties of opioid agonists by preventing the death of dopaminergic neurons, which are responsible for the dopamine release detected after a long exposure to morphine.