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Different mechanisms mediating tail-flick inhibition induced by beta-endorphin, DAMGO and morphine from ROb and GiA
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Abstract:
The effects of beta-endorphin, D-Ala2-NMePhe4-Gly-ol-enkephalin (DAMGO) and morphine microinjected into raphe obscurus nucleus (ROb) and gigantocellular reticular nucleus alpha (GiA) in inhibiting the tail-flick response were studied in pentobarbital anesthetized rats. beta-Endorphin (0.1-3 micrograms) microinjected into ROb inhibited the tail-flick response dose-dependently and produced 100% inhibition at high doses (greater than 3 micrograms). DAMGO [0.004-0.015 micrograms] injected into ROb, also dose-dependently, inhibited the tail-flick response but reached a plateau of 60 to 80% inhibition at high doses (greater than 0.015 micrograms). Morphine (10-60 micrograms) injected into ROb produced only a small inhibition (less than 20% inhibition) even at high doses (greater than 60 micrograms). The rank order of potency of these opioids on the tail-flick inhibition was DAMGO greater than beta-endorphin greater than morphine. Morphine (1-10 micrograms) and DAMGO (0.004-0.03 micrograms) microinjected into GiA produced dose-dependent inhibitions of the tail-flick response and high doses of these two mu agonists fully inhibited the tail-flick response. However, beta-endorphin (0.1-10 micrograms) injected into GiA produced a small but dose-dependent inhibition of the tail-flick response (less than 60% inhibition). The rank order of potency of these opioids on the tail-flick inhibition was DAMGO greater than beta-endorphin greater than morphine. The inhibition of the tail-flick response induced by beta-endorphin (2 micrograms) microinjected into ROb was blocked by the coadministration of beta-endorphin-[1-27] (6 micrograms), but not naloxone (1 microgram).(ABSTRACT TRUNCATED AT 250 WORDS)