Modification of morphine sensitization by opioid and dopamine receptor antagonists: evaluation by studying ambulation in mice.
The repeated administration of morphine (10 mg/kg s.c.) at 3- to 4-day intervals caused sensitization to its ambulation-increasing effect. A mu-opioid receptor antagonist naloxone (0.03-1 mg/kg s.c.), and dopamine D1 and D2 receptor antagonists SCH 23390; R-(+)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl (0.01-0.1 mg/kg s.c.) and YM-09151-2 (nemonapride); cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide (0.003-0.1 mg/kg s.c.), respectively, dose dependently reduced the ambulation increase caused by morphine as well as the sensitization to morphine, when one of them was combined with morphine in the repeated administration. Treatment with SCH 23390 or YM-09151-2, but not naloxone, 3 h after each morphine administration tended to enhance the morphine sensitization. Furthermore, when YM-09151-2 (0.1 mg/kg) was repeatedly administered to the morphine-naive mice 5 times at 3- to 4-day intervals, these mice showed a significant increase in morphine sensitivity. Although the morphine sensitization was partially reversible, repeated (5 times) treatment of the morphine-sensitized mice with SCH 23390 (0.1 mg/kg) resulted in a further enhancement in morphine sensitivity. The same treatment with YM-09151-2 (0.03 and 0.1 mg/kg) tended to increase the sensitivity. These results suggest that, in terms of ambulation in mice, an enhancement of dopaminergic neurotransmission through the agonistic action on mu-opioid receptors is responsible for induction of morphine sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
Kuribara
H
H
Department of Neurobiology and Behavior, Gunma University School of Medicine, Maebashi, Japan.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D016138:Walking
D001549:Benzamides; D001552:Benzazepines; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; C030265:nemonapride