Relationship between body temperature and brain monoamines during the development of tolerance to delat9-tetrahydrocannabinol in the rat.

The development of tolerance to delat9-tetrahydrocannabinol (delta9-THC) was examined. Rats with permanently indwelling intravenous catheters were injected daily with delta9-THC, 2 mg/kg, for up to 10 days and on each day subjective behaviour and body weight of each rat were noted. Tolerance appeared to develop to both the excitatory and depressant behavioural effects of delta9-THC, whereas the rate of gain in body weight of delta9-THC treated rats was retarded and tolerance to this phenomenon did not develop over the experimental period. On days 1, 2, 3, 5, 6, and 10 body temperature was recorded continuously for at least 2 h after delta9-THC and in other groups of rats the brain levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured spectrophotofluorimetrically 1 h after delta9-THC. Tolerance developed to the delta9-THC-induced hypothermia by day 3, and on days 6 and 10 hyperthermia was observed. delta9-THC did not markedly affect the brain levels of NA or DA over the experimental period. The brain levels of 5-HT were unchanged on days 1--5 but there was a decrease on days 6 and 10. On days 1, 2, and 3 brain levels of 5-HIAA were raised, whereas on day 6 there was a decrease. These results show that delta9-THC induces tolerance to the hypothermia and elevation of brain 5-HIAA levels in a linear manner. An inverse relationship appears to exist between these two parameters.