Peripheral Administration of Loperamide and Methylnaloxone Decreases the Degree of Anxiety in Rats

We studied the effect of mu-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. mu-Opioid receptor agonist loperamide had the most pronounced anxiolytic effect. Analysis of animal behavior in the forced swimming test showed that administration of mu-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, mu-opioid receptor agonist loperamide has the anti-anxiety properties and produced no sedative effect. Therefore, this agent holds much promise as an anxiolytic drug.