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 dynorphin, 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.
Katoh
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A
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Nabeshima
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T
Kameyama
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T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004347:Drug Interactions; D004399:Dynorphins / Q000031:analogs & derivatives / Q000494:pharmacology; D004723:Endorphins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D005082:Physical Exertion; D013312:Stress, Physiological; D013550:Swimming
D004723:Endorphins; D004745:Enkephalins; D010446:Peptide Fragments; C061285:E 2078; D004399:Dynorphins