Opioids are characterized by their ability to bind to opioid receptors mu (μ), kappa (κ), and delta (δ) and alter neural signal transmission [10, 11]. Opioid receptors are found in both the central nervous and peripheral nervous tissues [12]. They are distributed throughout the brain in varying concentrations depending on their classification, however all receptors are found to be highly abundant in the amygdala, the nucleus accumbens (NAc), and the caudate putamen (CP) [13]. These areas, as well as the ventral tegmental area (VTA), contain gamma-aminobutyric acid (GABA)-ergic interneurons that compose the complex neural circuitry involved in opioid dependence [14, 15]. Opioid receptors also differ in their binding affinities to specific ligands to induce varying degrees of analgesic effect and anti-nociception, in addition to other physiological effects [10, 12]. Endogenous opioid peptides, including enkephalins, β -endorphins, endomorphins and dynorphins, are mediated by their binding to opioid receptors [12, 16], and therefore play a role in modulating mood and regulating stress responses [11, 17, 18].
