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

The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by s olution hybridization in rats treated chronically with morphine or nal trexone. Morphine treatment (2 x 75 mg pellets were implanted SC on Da y 1 and 2 more on Day 4) resulted in the development of tolerance to m orphine's antinociceptive (analgesic) effect, as assessed by the hot p late procedure on treatment Day 7. Following the hot plate test, selec ted 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, hypothalam us, medial thalamus, or sensorimotor cortex. In a separate experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on C NS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease w as detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21% ), and medial thalamus (by 27%). Chronic exposure to morphine or naltr exone did not result in alterations in the sire of full-length MOR-1 m RNA 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 mo rphine do not involve concurrent changes in the steady-state levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a re gion-specific downregulation of MOR-1 mRNA levels, which may be second ary to the naltrexone-induced increase in mu receptor binding.