Relationship between body temperature and brain monoamines during the development of tolerance to ?9-tetrahydrocannabinol in the rat

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Abstract
The development of tolerance to Δ9-tetrahydrocannabinol (Δ9-THC) was examined. Rats with permanently indwelling intravenous catheters were injected daily with Δ9-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 exciatory and depressant behavioural effects of Δ9-THC, whereas the rate of gain, in body weight of Δ9-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 Δ9-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 Δ9-THC. Tolerance developed to the Δ9-THC-induced hypothermia by day 3, and on days 6 and 10 hyperthermia, was observed. Δ9-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 Δ9-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.