We studied the effect of μ-opioid receptor ligands on anxious and depressive behavior of rats. Intragastric administration of loperamide and methylnaloxone reduced animal anxiety evaluated by an increase in the number of entries into and time spent in open arms of the elevated plus-maze. μ-Opioid receptor agonist loperamide had the most pronounced anxiolytic effect. Analysis of animal behavior in the forced swimming test showed that administration of μ-opioid receptor antagonist methylnaloxone reduced the latency of the first submersion, increased the total time of submersion episodes, and shortened the time of active swimming, which attested to depressive properties of this agent. Loperamide had little effect on behavior of rats in the forced swimming test. Thus, μ-opioid receptor agonist loperamide has the antianxiety properties and produced no sedative effect. Therefore, this agent holds much promise as an anxiolytic drug.
β-Endorphin content in the extracellular space of rat cingulate cortex was measured using intravital microdialysis followed by ELISA. Intragastric administration of μ-opioid ligands loperamide and methylnaloxone not crossing the blood-brain barrier produced different effects on β-endorphin level: loperamide reduced and methylnaloxone significantly increased the release of β-endorphin into the extracellular space of rat cingulate cortex. Emotional stress caused by immobilization resulted in slight increase in β-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.
We studied the effect of peripheral μ- and κ-opioid receptor agonists (not crossing the bloodbrain barrier) on locomotor activity and metabolism in rats after acute administration of ethanol. Intraperitoneal injection of ethanol in a single dose of 2 g/kg had a strong depressive effect manifested in a decrease in horizontal locomotor activity and suppression of metabolism. μ-Opioid receptor agonist DAMGO and κ-opioid receptor agonist ICI 204,448 partly abolished the effect of ethanol on locomotor activity of rats. ICI 204,448 was most potent in this respect. In contrast to μ-opioid receptor agonist DAMGO, κ-opioid receptor agonist ICI 204,448 prevented metabolism suppression induced by ethanol. Our results indicate that ICI 204,448 significantly inhibits the depressive effect of ethanol. DAMGO showed only partial effectiveness under these experimental conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.