Attenuation of morphine dependence and withdrawal by glycine B site antagonists in rats.
Numerous data indicate that noncompetitive and competitive N-methyl-D-aspartate (NMDA) receptor antagonists inhibit the development of physical dependence on opioids when these substances are administered together, and NMDA receptor antagonists are used at lower range of doses. Higher doses of these antagonists can enhance some opioid-induced effects. The present study extends these findings to the effects of NMDA/glycine (glycine(B)) site antagonists. Wistar rats were rendered dependent on morphine by implantation of morphine pellets. Both of the glycine(B) site antagonists used, 7-chloro-4-hydroxy-3-(3-phenoxy)-phenyl-2(H)-quinolone (L-701,324; 2.5 and 5.0 mg/kg) and 5,7-dichlorokynurenic acid (5,7-DCKA; 25, 50, and 100 mg/kg), suppressed the expression of morphine withdrawal syndrome estimated as wet dog shakes. Furthermore, L-701,324 (2.5 and 5 mg/kg), given twice a day during the development of morphine dependence, attenuated the development of morphine dependence, and the results were comparable to those obtained after administration of noncompetitive NMDA receptor antagonist - MK801 (0.1 mg/kg). Our data suggest that glycine(B) site antagonists may attenuate wet dog shakes (withdrawal) and the development of dependence, both being induced by chronic morphine administration in rats.
Department of Pharmacodynamics, Medical University School, Staszica 4, PL-20-081, Lublin, Poland. jolka@panaceum.am.lublin.pl
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Kotlińska
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D009021:Morphine Dependence / Q000188:drug therapy*; D009270:Naloxone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects*; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D009292:Narcotic Antagonists; D009294:Narcotics; D015363:Quinolones; D018009:Receptors, Glycine; D009270:Naloxone; D016291:Dizocilpine Maleate; D009020:Morphine; D007736:Kynurenic Acid; C094635:L 701324; C066192:5,7-dichlorokynurenic acid