Time course of changes in mu-opioid receptor mRNA levels in the periaqueductal gray of rat brain by a single or repeated injections of antisense oligodeoxynucleotides

The effect of phosphorothioated antisense oligodeoxynucleotide (AS ODN) aga inst the mu-opioid receptor (MOR) on MOR mRNA level in the periaqueductal g ray (PAG) of rat brain was investigated. The MOR mRNA levels at 3, 6, 12, 2 4, 48 and 72 h after MOR AS ODN microinjection into the FAG were determined by reverse transcriptase-polymerase chain reaction. The MOR mRNA level was significantly decreased only at 12 h after the injection of 10 mu g MOR AS ODN. When 10 mu g MOR AS ODN was given three times at the interval of 48 h , MOR mRNA levels were significantly decreased at 6, 12 and 24 h after the last injection of the AS ODN. However, MOR mRNA levels were not significant ly changed by three injections at 48-h interval of MOR sense ODN or AS ODNs against delta- and kappa-opioid receptors, although the two latter AS ODNs significantly reduced the respective targeted mRNA levels. In conclusion, the present results show that the selective decrease in MOR mRNA is at leas t one reason why the reported diminished effects of MOR agonists are produc ed in animals pretreated with MOR AS ODN, although they could be produced t hrough several mechanisms in which MOR mRNA level does not change.