Inhibition of enkephalin degradation attenuated stress-induced motor suppression (conditioned suppression of motility).
Mice exhibit a marked suppression of motility when they are placed in the same cage in which they had previously received an electric shock. This suppression of motility is believed to be stress-induced and is a conditioned response. A decrease in the Met-enkephalin levels and a decrease in the dopamine (DA) turnover in the striatum of these "conditioned suppression" groups have been exhibited. The present study investigates whether inhibition of enkephalin degradation induced by an enkephalinase A and/or an aminopeptidase inhibitor attenuates a conditioned suppression of motility. The effects of thiorphan and bestatin, both alone and in combination, were investigated. Thiorphan alone (25, 50 and 100 micrograms i.c.v.) significantly attenuated the conditioned suppression of motility in a dose-dependent manner, but not bestatin (25, 50 and 100 micrograms i.c.v.) alone. The combination of these drugs (25 and 50 micrograms, each, i.c.v.) also significantly reduced the conditioned suppression of motility in a dose-dependent manner. The attenuation of conditioned suppression of motility induced by thiorphan and bestatin was antagonized by naloxone (5 mg/kg s.c.) and pimozide (100 micrograms/kg i.p.). In addition, the combination of thiorphan and bestatin reversed the decreases of Met-enkephalin levels and the decreases of DA turnover in the striatum in conditioned suppression group. These results suggest that attenuation of the conditioned suppression of motility induced by thiorphan and bestatin may be directly proportional to the increases of endogenous opioid peptide contents, and that the effect of these drugs may be related to the striatal DAergic system.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
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Nabeshima
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Katoh
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Kameyama
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin; D010868:Pimozide / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology*; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D004745:Enkephalins; D010868:Pimozide; D009270:Naloxone; D004744:Enkephalin, Methionine; D015244:Thiorphan; D008625:Tiopronin; D000626:Aminopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; D004298:Dopamine