Uliginosin B presents antinociceptive effect mediated by dopaminergic and opioid systems in mice

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 39; no. 1; pp. 80 - 87
• Main Authors: Stolz, Eveline Dischkaln, Viana, Alice Fialho, Hasse, Diego Rafael, von Poser, Gilsane Lino, do Rego, Jean-Claude, Rates, Stela M.K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2012; Elsevier
• Subjects: Analgesics - antagonists & inhibitors; Analgesics - pharmacology; Animals; Antinociceptive; Benzazepines - pharmacology; Biological and medical sciences; Brain; Brain - drug effects; Brain - metabolism; Dopamine; Dopamine Antagonists - pharmacology; Dopamine receptors; Drug Interactions; Hypericum; Male; Medical sciences; Mice; Mice, Inbred Strains; monoamines; Naloxone; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Neuropharmacology; Opioid receptors; Opioids; Pain Measurement - drug effects; Pain Measurement - methods; Pain Measurement - statistics & numerical data; Pain perception; Pharmacology. Drug treatments; Phloroglucinol; Phloroglucinol - analogs & derivatives; Phloroglucinol - antagonists & inhibitors; Phloroglucinol - pharmacology; Radioligand Assay - methods; Rats; Rats, Sprague-Dawley; Receptor mechanisms; Receptors, Dopamine - metabolism; Receptors, Opioid - metabolism; Rotarod Performance Test - statistics & numerical data; sulpiride; Sulpiride - pharmacology; Uliginosin B; SULP; DAMGO; DTT; Hypericum; Phloroglucinol; FEPPS; CGEN; GDP; SCH 23390; GTPγS; ULI; ANOVA; NMDA; COD; Antinociceptive; CIOMS; HPLC; TRPC6; 1H RMN; i.p; 13C RMN; p.o; MOR; HAL; GABA; NAL; SCH; SEM; RM; Uliginosin B; IBAMA; Hypericum perforatum; Pharmacognosy; Guttiferae; Rodentia; Opiates; Antitussive agent; Opioid peptide; Medicinal plant; Vertebrata; Mammalia; Analgesic; Mouse; Dicotyledones; Animal; Angiospermae; Spermatophyta; Dopaminergic pathway
• DOI: 10.1016/j.pnpbp.2012.05.012
• ISSN: 0278-5846

Previous studies have shown that uliginosin B inhibits dopamine reuptake in rat brain. This compound occurs in Hypericum polyanthemum and H. caprifoliatum for which was reported to have antinociceptive effect sensitive to naloxone. The aim of this study was to assess the antinociceptive effect of uliginosin B and to evaluate the involvement of opioid and dopaminergic receptors activation. Uliginosin B presented antinociceptive effect in hot-plate and abdominal writhing tests, in mice, at doses that did not impair the motor coordination (15mg/kg, i.p.). Uliginosin B in high dose (90mg/kg, i.p.) presented ataxic effect in the rotarod apparatus. These effects seem to be mediated by distinct receptors since the effect on the hot-plate was completely abolished by naloxone and sulpiride, but it was unaffected by SCH 23390. On the other hand, the motor impairment induced by uliginosin B was completely prevented by naloxone and partially prevented by sulpiride and SCH 23390. However, the receptors' activation appears to be indirect since uliginosin B did not bind to opioid and dopaminergic receptors. Thus, uliginosin B effects probably are due to its ability to inhibit monoamine reuptake with consequent activation of dopamine receptors and indirect stimulation of opioid system. ► Uliginosin B is a dimeric phloroglucinol from Brazilian Hypericum species. ► Uliginosin B induced antinociceptive and ataxic effects in mice. ► Activation of opioid, D1 and D2 receptors underlies uliginosin B effects in vivo. ► Uliginosin B did not alter [35S]-GTPγS binding to thalamus and striatum membranes. ► Uliginosin B did not alter [3H]-naloxone, [3H]-SCH 23390 and [3H]-sulpiride binding.