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.
D000700:Analgesics; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats
D000700:Analgesics; D009020:Morphine; D006220:Haloperidol; D004298:Dopamine