Effects of stress on opioid receptor binding in the rat central nervous system

Abstract

The endogenous opioid peptides are known to play a significant role in the modulation and or mediation of numerous environmental or experimental Stressors. However, the specific opioid peptide(s) and receptor type(s) involved, under what physiologic conditions they are engaged and within which regions of the CNS is not well understood. We therefore examined the effects of both a chronic and an acute Stressor 90-h water deprivation and a single 20-min foot shock on opioid receptor binding in 17 specific rat brain nuclei. [ 3H]DSTLE (Tyr-D-Ser-Gly-Phe-Leu-Thr) and [ 3H]DAGO(Tyr-D-Gly-Phe- NMe-Phe-Gly-ol) were used to label delta and mu receptors, respectively. Foot shock induced profound antinociception as measured by tail-flick latency which outlasted the Stressor by several minutes. However, only the septum responded with a decrease in [ 3H]DAGO binding to this type of stress-induced analgesia. No other alterations in either [ 3H]DAGO or [ 3H]DSTLE binding were seen in response to foot shock. In contrast, water deprivation induced increases in [ 3H-DAGO] binding in the septum as well as increases in [ 3H]DSTLE binding in the caudate and accumbens nuclei. Moreover, the presumptive mild stress of handling in the foot shock control group was sufficient to decrease mu or delta receptor binding in seven out of 17 brain regions investigated (including the frontal cortex and olfactory tubercle where both mu and delta binding were increased) when compared to unhandled deprivation control animals. These changes in opioid receptor binding may have been the result of alterations in treatment-induced peptide release, receptor regulation, or interactions with other released ncurotransmitter ligand receptor complexes. Most of the brain regions displaying significant alterations in receptor binding (e.g. amygdala, cingulate, frontal cortex, olfactory tubercle and nucleus accumbens) are either components of, or are associated with the limbic system. These data implicate limbic opioid activation as a consequence of various stressors and may therefore be reflective of a role for opioids in the emotional/motivational aspects of stress.