NUCLEIC ACID SYNTHESIS IN BRAINS FROM RATS TOLERANT TO MORPHINE ANALGESIA

¹ Pharmacology-Toxicology Section, Midwest Research Institute, Kansas City, Missouri

Tolerant and nontolerant rats were divided into two subgroups. One subgroup was injected intracerebrally with 1 c of thymidine-2-¹⁴C (specific activity, 58.3 mc/mmol) and the other with 1 c of orotic acid-6-¹⁴C (specific activity, 7.2 mc/mmol) prior to their last injection of morphine sulfate or saline. Rats from each subgroup were killed at 1, 4, 12, 24 and 48 hours and brain deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) extracted and counted. Specific activities of brain DNA in tolerant and nontolerant rats were maximal at four hours. This was followed by a decrease in DNA specific activity in both groups at 12 hours, which may reflect a nocturnal event. Specific activities returned to maximal levels at 24 and 48 hours. No treatment-related effects were observed. specific activity of RNA in the nontolerant rats was maximal by 24 hours and fell 30 to 40% by 48 hours. Similarly, the specific activity of brain RNA from tolerant rats was maximal at 24 hours, but remained elevated significantly at 48 hours. This apparent change inthe disappearance rate of newly formed RNA-¹⁴C could be visualized in the hippocampus. Tolerance to morphine analgesia remained maximal 60 hours after the last injection and no overt signs of withdrawal were observed. A possible relationship between RNA and morphine is discussed.