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.
Przewłocka
B
B
Department of Neuropeptides Research, Polish Academy of Sciences, Kraków.
Sumová
A
A
Lasoń
W
W
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D044482:Benzeneacetamides; D003214:Conditioning, Classical; D004597:Electroshock; D004723:Endorphins / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D005239:Fear / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism
D000700:Analgesics; D014150:Antipsychotic Agents; D044482:Benzeneacetamides; D004723:Endorphins; D011498:Protein Precursors; D011743:Pyrimidines; D011759:Pyrrolidines; D001615:beta-Endorphin; C025681:alpha-neoendorphin; C043077:ipsapirone; D009020:Morphine; C045444:U 69593