Research studies have defined the important role of endogenous
opioids in modulating stress-associated behavior. The release of β-
endorphins in the amygdala in response to stress helps to cope with a stressor by inhibiting the over-activation of HPA axis. Administration of mu
opioid agonists reduces the risk of developing
post-traumatic stress disorder (
PTSD) following a traumatic event by inhibiting fear-related memory consolidation. Similarly, the release of endogenous
enkephalin and
nociceptin in the basolateral amygdala and the nucleus accumbens tends to produce the anti-stress effects. An increase in
dynorphin levels during prolonged exposure to stress may produce learned helplessness, dysphoria and depression. Stress also influences
morphine-induced conditioned place preference (
CPP) depending upon the intensity and duration of the stressor. Acute stress inhibits
morphine CPP, while chronic stress potentiates
CPP. The development of dysphoria due to increased
dynorphin levels may contribute to chronic stress-induced potentiation of
morphine CPP. The activation of ERK/
cyclic AMP responsive
element-binding (CREB) signaling in the mesocorticolimbic area,
glucocorticoid receptors in the basolateral amygdala, and
norepinephrine and
galanin system in the nucleus accumbens may decrease the acute stress-induced inhibition of
morphine CPP. The increase in
dopamine levels in the nucleus accumbens and augmentation of GABAergic transmission in the median prefrontal cortex may contribute in potentiating
morphine CPP. Stress exposure reinstates the extinct
morphine CPP by activating the
orexin receptors in the nucleus accumbens, decreasing the
oxytocin levels in the lateral septum and amygdala, and altering the GABAergic transmission (activation of GABAA and inactivation of GABAB receptors). The present review describes these varied interactions between
opioids and stress along with the possible mechanism.