The Use of Animal Models to Measure Tolerance, Dependence, and Abuse Potential

Despite the signicant inuence of mu, kappa, and delta opioid receptors on thermoregulation, effects of kratom alkaloids on body temperature have not been investigated. Based on the rich history of using body temperature assays to dene the pharmacological prole of novel opioids, it can be predicted that much could be learned about the prole of mitragynine and its derivatives by dening their effects on body temperature. Much of the early work investigating a role for opioid receptors in thermoregulation was accomplished with morphine. The administration of morphine

to rats at doses of 4-15 mg/kg morphine produces robust hyperthermia, but progressively higher doses induce hypothermia (Geller et al. 1983). Experiments using selective opioid receptor agonists and antagonists reveal that mu opioid receptor activation is responsible for the hyperthermic response to morphine, whereas kappa opioid receptor activation mediates the hypothermic effect of morphine (Spencer et al. 1988; Handler et al. 1992; Adler and Geller 1987, 1993; Adler 1983; Geller et al. 1986).