The effect of an endogenous compound 1-methyl-1,2,3,4,-tetrahydroisoquinoline on morphine-induced analgesia, dependence and neurochemical changes in dopamine metabolism in rat brain structures.
1,2,3,4-Tetrahydroisoquinolines, among them the most interesting neuroprotective substance, an inhibitor of MAO, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), are endogenous compounds present in the central nervous system of mammals and humans. In this study, we investigated the effect of 1MeTIQ on morphine-induced analgesia, tolerance and abstinence syndrome as well as its effect on morphine-induced changes in dopamine metabolism in rat brain structures (nucleus accumbens, striatum, substantia nigra) using HPLC methodology. The experiments were carried out on male Wistar rats. Morphine analgesia was measured in the "hot-plate" test. To induce tolerance, morphine was given chronically (20 mg/kg i.p.) alone or following 1MeTIQ (50 mg/kg i.p.) injection. The development of dependence was assessed in the naloxone (2 mg/kg i.p.) precipitation test, after 10 days of morphine administration. The behavioral studies have shown that an endogenous compound, 1MeTIQ produced strong potentiation of morphine analgesia, prevented the development of morphine tolerance and inhibited expression of morphine abstinence syndrome in morphine-dependent rats. In neurochemical studies, we have demonstrated that 1MeTIQ antagonized morphine-induced changes in dopamine metabolism observed in rat brain structures. The main finding of this study was demonstration for the first time of an anti-abuse effect of an endogenous compound, 1MeTIQ, and its efficiency in counteracting morphine-induced addiction in the way useful from clinical point of view. The obtained results suggested a possibility of clinical application of 1MeTIQ in morphine addiction.
Wasik
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A
Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Romańska
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I
Antkiewicz-Michaluk
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L
D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D000701:Analgesics, Opioid; D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; D009270:Naloxone; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; D009020:Morphine; D002118:Calcium; D004298:Dopamine