Effects Of Delta-opioid Receptor Agonists On Severe Forebrain Ischemia In Rats

Objectives: To explore the neuroprotective effects of delta-opioid receptor agonists（DADLE，[D-Ala2,D-Leu5]-enkephalin）on the severe forebrain ischemia in rats.Methods: Sixty adult healthy male rats were equally and randomly distributed into sixgroups: sham operation group (sham), artificial cerebral spinal fluid group (ACSF);DADLE0.2mmol/L group (DAD0.2); DADLE2mmol/L group (DAD2); DADLE20mmol/L group (DAD20) and DADLE2mmol/L+naltrindole2mmol/L group (DAD2+N).With a stereotaxic instrument an injection containing above-mentioned solution wasinjected into lateral cerebral ventricle. After45min, rats were subjected to10min of severeforebrain ischemia. Score of motor function, behaviors changes and histologic outcomeswere measured in five days later.Results: The score of motor function in the ACSF group was significant lower thanother groups (P<0.05). There were significant differences among DAD0.2, DAD2andDAD20group (p<0.05). The highest score was found in DAD20group. The score in theDAD2+N group was lower than in the DAD2group (p<0.05). The latent period in the7thand8th days in the ACSF group was longer than any other group (p<0.05), and there weresignificant differences among DAD0.2, DAD2and DAD20group (p<0.05). The latentperiod was the shortest in DAD20group. The latent period in the DAD2+N group waslonger than in the DAD2group (p<0.05). The swimming speed had no significantdifference among groups (p>0.05). The time spent in the target quadrant in the ACSFgroup was shorter than any other group (p<0.05), and there were significant differencesamong DAD0.2, DAD2and DAD20group (p<0.05). There was the longest swimmingtime in DAD20group. The time spent in the target quadrant in DAD2+N group was shorter than that in DAD2group (p<0.05). The number of survival neurons was least inACSF group compared with any other group in the CA1area of hippocampus (p<0.05),and there were significant differences among DAD0.2, DAD2and DAD20group (p<0.05).The most number of survival neurons was found in DAD20group. The survival neurons inDAD2+N group were less than that in DAD2group (p<0.05).Conclusions：Injection of DADLE in the lateral cerebral ventricle have a dosedependently neuroprotective effect on severe forebrain ischemia in the rats, which partlydue to the activation of delta opioid receptor.