The Purpose of this study was to determine the effect of repeated morphine administration on opioid peptides and kappa receptor
gene mRNA levels in specific brain regions related with rewarding and aversive properties. Male Wistar rats were given 6 consecutive subcutaneous
injection of morphine sulfate (6.25 mg/ kg) or normal saline (1 ml/ kg) at 2 hour intervals. Thirty min after final injection, the whole brain (except cortex, cerebellum and lower brain stem) and regions of interest were dissected. Using a quantitative solution hybridization protection assay for mRNA levels (pg mRNA/ μg total RNA ), we detected: 1. the
concentration of preprodynorphin for morphine treated vs normal saline control group in the whole brain 1.34 ±0.06 vs 0.82±0.14(ANOVA, P<0.01), in nucleus accumbens 8.41±1.39 vs 10.28±0.67 (P=0.26) and in caudate putamen 7.88±0.50 vs 6.23±0.38 (P<0.05); 2. the concentration of preproenkephalin for morphine treated vs normal saline control group in the whole brain 8.33± 0.51 vs 8.84±1.37 (P=0.73), in nucleus accumbens 18.62±1.96 vs 20.37±2.23 (P=0.58) and in caudate putamen 37.07±2.81 vs 29.62±3.09 (P=0.11); 3. the concentration of kappa receptor for the 2 groups in the whole brain 0.70±0.07 vs 0.47±0.02 (P<0.01), in caudate putamen 1.51±0.19 vs 1.76±0.34 (P=0.54) and in substantia nigra 0.36±0.07 vs 0.66±0.11 (P=0.05, marginally significant). The data first indicated that brain dynorphin κ receptor system may be involved in the development of acute morphine tolerance, and that repeated morphine injection may effect dynorphine κ system in brain nuclei associated with rewarding and aversion.