The influence of haloperidol pretreatment on the morphine toxicity

The influence of dopaminergic modifiers on morphine-induced analgesia and lethality was studied comparing both the effect of a single pre-dose of haloperidol and and continuous pretreatment for three weeks with haloperidol. A single administration of haloperidol enhanced morphine-induced analgesia probably due to the receptor blocking action of haloperidol which supports the reduction of dopamine release produced by morphine. The daily haloperidol administration for 3 weeks however decreased the analgesic action of morphine in consequence of a dopamine receptor supersensitivity developed in this time. The lethality was increased under both conditions. These results suggest that the dopaminergic system, dependent upon its sensitivity, plays a modulating role in morphine-induced analgesia, but not in morphine-induced lethality.