The effects of parachlorophenylalanine on nontolerant rats and of cholinergic blocking drugs on toleaant rats to morphine.

The small amounts of morphine raise while the large amounts of morphine lower the body temperature of non-tolerant rat. On the other hand, morphine raise and its antagonist, nalorphine, lower the body tem perature of tolerant rat (1-3). Feldberg and Meyers presented the new concepts that norepinephrine and 5-hydroxytryptamine (5-HT) in hypothalamus regulate the body temperature (4-6). Collier (7) and Sharpless and Jaffe (8) are making efforts to explain the phenomena of tolerance, depend ence and abstinence syndrome by pharmacological denervated supersensitivity (disuse supersensitivity). Their theories are based on the existence of interaction between morphine and humoral transmitters in the brain. These evidences mentioned above stimulate us to study the relationship between morphine and humoral transmitters. In the present investigation, the changes of body temperature and spontaneous activity of rat were chosen as the indicators resulting from the interaction between morphine and humoral transmitters. Thermistor probe was inserted 6 cm into rectum of the male rat of Donryu strain and taped on the tail. Rat can move relatively freely during measuring body temperature without touching and knowing what is being done. Under these conditions, the rectal temperature of the rat was measured outside of the chamber, the temperature of which is maintained at 20+0.5°C and the relative humidity at 70±10%. The body temperature of non-tolerant rat was lowered significantly by the subcutaneous (s.c.) adminis tration of 50 mg/kg of morphine-HCI, while this lowering action was completely prevented by the pretreat ment with parachlorophenylalanine (300 mg/kg, i.p.) 72 hours before morphine injection. Parachloro phenylalanine is known to lower 5-HT level in brain to about 10% of normal without decreasing norepine phrine level in brain significantly (9) and has no effect on the body temperature of rats by its administration.