Biological mechanisms of the individual variability of the anxiolytic action of opioids

The opioid system is one in a number of peptidergic regulatory systems that support an appropriate anxiety level. The drugs that interact with the opioid system have been shown to influence anxiety, although there is a notable variability in their pharmacological effects. Biological mechanisms of this variability are considered to be the heterogeneity of opioid receptors, the ratio of the processes of their expression and desensitization, and the balance between the synthesis and degradation of endogenous opioid peptides. For instance, the anxiolythic effect of the synthetic derivate of enkephalin in rats was detected after stress-induced exhaustion of endogenous opioids, and its efficacy depended on the degree of delta- and mu-opioid receptor desensitization in some brain regions. The anxiolythic properties of the heptapeptide Selanc that has also been shown to affect the opioid system are most prominent in subjects with elevated activity of enzymes degrading endogenous opioid peptides. Thus, delicate correction of the opioid system with drugs of peptide nature is supposed to become a new approach to treatment of some forms of anxiety disorders accompanied with exhaustion of the endogenous opioid system and, in particular, of generalized anxiety disorder.