A study of prodynorphin in the periamygdaloid cortex of humans with heroin addiction found that prodynorphin levels were significantly reduced. Further tests were run to determine the link of heroin metabolites to the prodynorphin to rule out ambiguity, but these tests led researchers to confirm that these decreases in prodynorphin were due to chronic heroin use and not a secondary factor.[1] The mRNA-prodynorphin expression of rats undergoing heroin self-administration showed similar results which, paired with tests of affect, indicate that prodynorphin expression in the periamygdaloid cortex of rats correlates with negative affect.[4] With the rat model results in mind, the study's results suggest that human opiate addicts have a lessened ability to manage negative affect due to the effects of heroin on the periamygdaloid cortex.