The influence of conditioned fear-induced stress on the opioid systems in the rat.
In this study the rats were repeatedly placed in a conditioning box, and 30 min later were subjected to a mild foot-shock. Anticipation of painful stimuli resulted in development of antinociception before a painful stimulus was applied. This conditioned fear-induced antinociception was antagonized by naloxone (1 mg/kg IP), as well as by ipsapirone (10 mg/kg IP), as measured by a tail-flick test. Stressed rats were hypersensitive to the analgesic action of morphine (1 mg/kg SC), but not to the specific kappa agonist U69,593 (0.1 mg/kg SC). In order to determine the involvement of the proopiomelanocortin and prodynorphin systems in stress we measured levels of their represenative peptides beta-endorphin and alpha-neoendorphin using selective RIAs. Biochemical data showed that conditioned stress evoked a marked decrease in the beta-endorphin level in the hypothalamus and both lobes of the pituitary, together with a three-fold increase in the peptide level in the plasma. In contrast, the level of alpha-neoendorphin in the hypothalamus, pituitary and spinal cord remained unchanged. Only in the plasma a decrease in that peptide content was found. Furthermore, in vitro studies showed that the spontaneous and K(+)-stimulated release of beta-endorphin from the hypothalamus of rats which had been exposed to a conditioned stimulus was enhanced, whereas the release of alpha-neoendorphin from that tissue was attenuated. These results suggest a major role of the proopiomelanocortin system and, to the lesser extent, of the prodynorphin one in the mechanism of a conditioned fear-induced stress.