Behavioral changes induced by stressful situations: Effects of enkephalins, dynorphin, and their interactions

Effects of opioid peptides on behavioral changes induced by stressful situations were investigated. [D-Ala²,Met⁵]-enkephalinamide and [D-Ala²,D-Leu⁵]-enkephalin, degrading-enzyme-resistant derivatives of methionine-enkephalin and leucine-enkephalin, respectively, significantly attenuated both environment-induced conditioned suppression of motility and forced swimming-induced immobility in a dose-dependent manner. The [D-Ala²,Met⁵]-enkephalinamide- and [D-Ala²,D-Leu⁵]-enkephalin-induced attenuations were antagonized by naloxone at different doses. In contrast, dynorphin A(1-17) and [N-methyl-Tyr¹, N-methyl-Arg⁷, D-Leu⁸]-dynorphin A(1-8) ethylamide (E 2078), a degrading-enzyme-resistant derivative of dynorpin, significantly potentiated both behavioral changes. The dynorphin- and E 2078-induced potentiations were inhibited by Mr 2266. [D-Ala²,Met⁵]-enkephalinamide-induced attenuation of environment-induced conditioned suppression of motility and forced swimming-induced immobility was prevented by treatment with dynorphin and E 2078 at the doses that did not affect the behavioral changes. This antagonism by both dynorphin and E 2078 was inhibited by Mr 2266. However, [D-Ala²,D-Leu⁵]-enkephalin-induced attenuation of both behavioral changes was not affected by either dynorphin or E 2078. These results indicated that activation of the methionine- or leucine-enkephalinergic system attenuates behavioral changes induced by stress, whereas activation of the dynorphinergic system potentiates those changes. Furthermore, the dynorphinergic system may interact with the methionine-enkephalinergic system, but not with the leucine-enkephalinergic system.