The role of histaminergic-noradrenergic axis in naloxone-induced withdrawal symptoms in mice.
The effects of histamine antagonists on naloxone-precipitated withdrawal symptoms were studied in morphine-dependent mice. Chlorpheniramine (0.5-10 mg/kg), a H1-blocker, given 1P 30 min before naloxone challenge produced a dose-dependent potentiation of withdrawal body weight loss, burrowing, and hypothermia, but did not influence either jumping or wet-dog shakes. On the other hand, cimetidine (10-100 mg/kg), a H2-blocker, produced dose-dependent potentiation of withdrawal hypothermia and jumping. Cimetidine was without effect on wet-dog shakes, burrowing, and body weight loss. The effect of chlorpheniramine was investigated in mice injected with 6-hydroxydopamine (6-OHDA) intracerebrally to examine whether histamine-mediated effects are some-how linked to noradrenergic pathways. Intracerebral injection of 6-OHDA in 5-day-old mice pups resulted in hyperlocomotion by the end of 30 days before initiation of morphine dependence. Mice pretreated with 6-OHDA developed a higher degree of naloxone-induced withdrawal jumping than nontreated mice. 6-OHDA (50 micrograms) lesions completely blocked the potentiating effect of chlorpheniramine on burrowing, hypothermia, and even reversed the effect on body weight loss. These findings suggest that both histamine H1- and H2-receptors may be involved in the expression of precipitated withdrawal in morphine-dependent mice and histamine receptors function as modulators of noradrenergic neurotransmission.
el Kadi
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AO
Department of Pharmacology, Faculty of Medicine, Al-Arab Medical University, Benghazi, Libya.
Sharif
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SI
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000503:physiopathology / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology; D013565:Sympatholytics / Q000494:pharmacology; D015431:Weight Loss / Q000187:drug effects
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D009292:Narcotic Antagonists; D013565:Sympatholytics; D009270:Naloxone; D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D016627:Oxidopamine; D009638:Norepinephrine