Attenuation of morphine tolerance and dependence by alpha-melanocyte stimulating hormone(alpha-MSH). |
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Authors: | J I Székely E Miglécz Z Dunai-Kovács I Tarnawa A Z Rónai L Gráf S Bajusz |
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Institution: | Research Institute for Pharmaceutical Chemistry, H-1325 Budapest, P.O. Box 82., Hungary |
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Abstract: | Repeated administration of morphine resulted in significant reduction of its analgesic potency. If 0.1 mg/kg α-MSH was coadministered, the tolerance development was attenuated, 1 mg/kg MIF (MSH release inhibiting factor), given simultaneously with morphine, did not affect tolerance. Injecting, however, MIF 1 hour prior to the daily opiate treatment resulted in accelerated development of tolerance supposedly by lowering the plasma α-MSH level at the time of morphine administration. Of the morphine abstinence symptoms the naloxone-induced jumping in morphine pretreated mice could not be modified either by α-MSH coadministration or by MIF pretreament, but the withdrawal body weight loss was found to be diminished by the former and increased by the latter peptide. The possible role of α-MSH in preventing the development of tolerance to the analgesic effect of endogenous opioid peptides is discussed. |
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