Changes in β-Endorphin Level in the Cingulate Cortex in Rats after Peripheral Loperamide and Methylnaloxone Administration at Rest and during Emotional Stress

beta-Endorphin content in the extracellular space of rat cingulate cortex was measured using intravital microdialysis followed by ELISA. Intragastric administration of mu-opioid ligands loperamide and methylnaloxone not crossing the blood-brain barrier produced different effects on beta-endorphin level: loperamide reduced and methylnaloxone significantly increased the release of beta-endorphin into the extracellular space of rat cingulate cortex. Emotional stress caused by immobilization resulted in slight increase in beta-endorphin level in the cingulate cortex. Peripheral administration of loperamide (but not methylnaloxone) significantly increased the release of the neuropeptide during stress. These findings support our hypothesis of reciprocal interaction between the central and peripheral compartments of the endogenous opioid system and provide explanations for the anti-stress effects of loperamide.