Antinociceptive action of opiates and opioid peptides after unilateral microinjection into area tempestas in rats.
Area tempestas (AT) is a forebrain area involved in the genesis and generalization of clonic convulsions in rats. This study reports that upon AT application opiates and opioid peptides produce antinociceptive effects as measured with the hot-plate (HP) and tail-flick (TF) tests in rats. Unilateral infusion of mu and kappa agonists into AT at doses in the nanogram range delayed the latency to respond for the contralateral paws in the HP test (Emax, 67-91 degrees of analgesia), beginning 1 to 5 min after application. A smaller effect was observed after the Leu-enkephalin, [D-Ala2,D-Leu5][enkephalin and D-Pen2,D-Pen5]enkephalin. No effect was observed after Met-enkephalin. In the TF test, unilateral application of mu and kappa agonists in the nanogram range produced antinociception with Emax values of 43 to 62 degrees of analgesia, beginning 5 to 15 min after infusion. No significant effect was found after unilateral infusion of delta agonists. Infusion into AT (10 min before) of naltrexone (2-4 ng), ICI 154, 129 (1-10 ng) and WIN 44,441-3 (2-20 ng) antagonized the antinociception evoked by locally applied morphine (25 ng), [D-Pen2,D-Pen5]enkephalin (50 ng) and U 50,488 (100 ng), respectively. In addition, antinociception induced by systemic morphine (2.5 mg/kg sc) was antagonized by subsequent (23 min) unilateral application of naltrexone (15 ng). In the HP test, a reduction of the antinociceptive effect of morphine was obtained for both ipsilateral and contralateral paws after the antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
d'Amore
A
A
Laboratorio di Farmacologie, Istituto Superiore di Santia', Roma, Italy.
Lorenzini
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P
Massotti
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M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004361:Drug Tolerance; D004723:Endorphins / Q000494:pharmacology* / Q000502:physiology; D004743:Enkephalin, Leucine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement; D016548:Prosencephalon / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism
D004723:Endorphins; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D004743:Enkephalin, Leucine; D009020:Morphine