CNS LEVELS OF MU-OPIOID RECEPTOR (MOR-1) MESSENGER-RNA DURING CHRONIC TREATMENT WITH MORPHINE OR NALTREXONE

The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by solution hybridization in rats treated chronically with morphine or naltrexone. Morphine treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4) resulted in the development of tolerance to morphine's antinociceptive (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7. Following the hot plate test, selected CNS regions were obtained by microdissection. The levels of MOR-1 mRNA in pg/mu g RNA ranged from 0.7 in sensorimotor cortex to 15.3 in medial thalamus. MOR-1 mRNA levels were not altered in the dorsal horn of spinal cord, nucleus raphe magnus, periaqueductal grey, hypothalamus, medial thalamus, or sensorimotor cortex. In a separate experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on CNS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease was detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21%), and medial thalamus (by 27%). Chronic exposure to morphine or naltrexone did not result in alterations in the sire of full-length MOR-1 mRNA from rat brain, or in the size of the region protected by the MOR-1 riboprobe (i.e., the entire coding region). Thus, the neuroadaptive processes associated with the development of analgesic tolerance to morphine do not involve concurrent changes in the steady-state levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a region-specific downregulation of MOR-1 mRNA levels, which may be secondary to the naltrexone-induced increase in mu receptor binding.