Interactions between anticholinesterase poisoning and opioid analgesia and locomotion in mice

Interactions between anticholinesterases and opioid drugs on antinociception and locomotor behaviour have been studied in the mouse. The anticholinesterase di-isopropylfluorophosphate (DFP) (1 mg/kg), pyridostigmine (1 mg/kg) and neostigmine (200 micrograms/kg) or drugs used to treat anticholinesterase poisoning (atropine, pralidoxime and diazepam) were not antinociceptive. DFP, at doses which produced marked neurotoxicity (2 mg/kg), produced antinociception which was not mediated by opioid receptors. The antinociceptive effects of alfentanil, but not fentanyl or morphine, were potentiated by DFP, whereas pyridostigmine and neostigmine were without effect. The potentiating activity of DFP was unaffected by atropine, pralidoxime and diazepam. DFP (1 mg/kg) produced a small degree of hypolocomotion whilst atropine and pralidoxime produced marked hyperlocomotion. Diazepam alone and with DFP, atropine, pralidoxime or opioid drugs produced marked motor incapacitation. Hyperlocomotion induced by morphine and alfentanil was reduced by DFP but fentanyl hyperlocomotion was unaffected. Treatment of DFP toxicity with atropine and pralidoxime reversed the effects on alfentanil locomotion but failed to alter DFP's action upon morphine or fentanyl locomotion. Atropine and pralidoxime treatment alone did not affect fentanyl hyperlocomotion, attenuated alfentanil hyperlocomotion and produced marked hypolocomotion in morphine-treated mice. Opioids and anticholinesterases do not exhibit common interactions and their effects are dependent on both opioid, anticholinesterase and the behaviour studied.