TABLE 1

Morphine and fentanyl differentially modulate the expression of miRNAs

Rat primary cultures were treated with PBS, 1 μM morphine, or 10 nM fentanyl for 3 days. CD1 mice were infused with saline (control), 12 μg/h morphine (1 ED50 dose/ 5 h), or 0.31 μg/h fentanyl (1 ED50 dose/2 h) for 3 days by using a micro-osmotic pump. Microarray experiments were performed in rat primary cultures (three times), mouse hippocampi (three times), and mouse cerebella (Cere. two times). The results were analyzed as described under Materials and Methods. The identified miRNAs have conserved sequences in human, mouse, and rat. Their expression was modulated by agonists in rat primary cultures and mouse hippocampi but not in mouse cerebella. The expression of these miRNAs was also measured by using real-time PCR in rat primary cultures and mouse hippocampi. Real-time PCR results were repeated four times and had P values less than 0.05. Data were analyzed by one-way ANOVA with post hoc Dunnett test for comparisons. Values presented are percentages of control values.

Long-Term TreatmentMicroarray for miRNAsReal-Time PCR
PrimaryHippocampiCerebellaPrimaryHippocampi
%%%%%
Morphine
    miR-224137162109131 ± 12127 ± 7
    miR-33113112795176 ± 23152 ± 8
    miR-365129126101125 ± 13120 ± 9
    miR-20a132132110143 ± 21128 ± 9
Fentanyl
    miR-224147172101135 ± 14154 ± 23
    miR-33112813191120 ± 11131 ± 11
    miR-36519412998176 ± 33143 ± 27
    miR-18476568884 ± 863 ± 23
    miR-190686510355 ± 1870 ± 6
    miR-301794910970 ± 853 ± 17