Morphine pretreatment (2.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 3 h later, but enhanced the antagonistic potency of naloxone. 2. Pretreatment with chlorpromazine slightly potentiated the antinociceptive effect of morphine measured 3.5 h later. The antagonistic effect of naloxone was also enhanced. 3. The observed effect of chlorpromazine on naloxone potency was augmented when naloxone was administered in the pretreatment regime. 4. The enhanced naloxone potency induced by morphine pretreatment was inhibited by chlorpromazine administered 0.5 h before the morphine pretreatment. 5. Adrenalectomy sensitized the animals to the antinociceptive effect of morphine. However, the naloxone potency was similar to that of the sham-operated controls. 6. Adrenalectomy greatly attenuated the effect of chlorpromazine pretreatment on naloxone potency. However, the effect of combined pretreatment with either chlorpromazine plus naloxone or morphine remained unaffected. 7. These results indicate that the increased naloxone potency after chlorpromazine pretreatment may be partly mediated through an adrenal-linked process. However, it appears that this process is not essential for the development of increased naloxone potency induced by morphine pretreatment and for the interaction between chlorpromazine, naloxone and morphine.
