Chronic adolescent stress attenuates morphine-induced antinociception and central amygdala neuronal activation in adult Wistar rats.

Stress exposure during critical developmental periods has been shown to increase the risk for an array of psychological and physiological pathologies in adulthood, including substance use disorder and chronic pain. Although incompletely understood, studies have suggested that stress alters opioid responses which in turn is associated with increased nociceptive and decreased antinociceptive responsivity. Previous studies demonstrating stress-induced attenuation of morphine antinociception used stress exposure models that included physical injury limiting generalization of the available findings. The aim of the current study was to characterize the effects of chronic adolescent psychosocial stress on morphine-induced antinociception and neuronal activation. Male and female Wistar rats were exposed to chronic adolescent stress (CAS) and tested in adulthood for either antinociceptive response to morphine or morphine-induced expression of cFos in the central nucleus of the amygdala (CeA) and ventrolateral periaqueductal gray (vlPAG). A history of CAS attenuated morphine-induced antinociception in the warm water tail withdrawal test for both sexes, demonstrating an effect of adolescent stress on responses to opioids in adulthood, regardless of sex. Similarly, CAS history caused a blunted response to morphine-induced cFos expression in the CeA, but not in the vlPAG for both sexes. Collectively, these data suggest that CAS exposure renders opioid analgesics less effective, and that this alteration is associated with altered responsivity to opioids in the CeA. Additional work identifying the mechanisms mediating stress-induced changes in opioid signaling are warranted, having the potential to influence pain management strategies for individuals with developmental stress histories.