Alteration in transcripting the gene encoding the δ-opioid receptor in rat brain is not underlying the development of tolerance to [D-Ala²,D- Leu⁵] enkephalin

Previous study has demonstrated that chronic treatment of [D-Ala², D- Leu⁵] enkephalin (DADLE) induces profound down-regulation of delta opioid receptor in rat brain. We further examined whether this down-regulation of receptor was due to a decrease in the transcription of gene encoding delta- opioid receptor (DOR-1). Rats received daily i.c.v. injection of DADLE for 1, 3, or 5 days and developed significant tolerance to the antinociceptive effect of DADLE after one-day treatment. We measured the level of mRNA in rat brain tissues using in situ hybridization. No significant changes in the mRNA levels of the cortex, striatum, hippocampus, and thalamus on any examined days were found as compared to those of rats received sham operation only. There is only a transient decrease of DOR-1 mRNA level in midbrain region that occurred after a three-day treatment. Thus, the result of this study did not suggest that alteration in transcription of gene-encoding delta-opioid receptor was responsible for the down-regulation of delta-opioid receptor associated with the development of tolerance to DADLE.