title: Tramadol reduces the 5-HTP-induced head-twitch response in mice via the activation of mu and kappa opioid receptors.
abstract: Tramadol, an atypical opioid analgesic, stimulates both opiatergic and serotonergic systems. Here we have investigated the effect of tramadol in mice on 5-hydroxyptrytophan (5-HTP)-induced head twitch response (HTR), which is an animal model for the activation of the CNS 5-HT(2A) receptors in mice. Tramadol attenuated 5-HTP-induced HTR in a dose-dependent manner as morphine. Furthermore, the nonselective opioid receptor antagonists, naloxone and diprenorphine (M5050), reversed the effect of tramadol on 5-HTP-induced HTR dose-dependently. Interestingly, in contrast to the selective delta opioid receptor antagonist NTI, beta-FNA, a selective mu receptor antagonist, and nor-BNI, a selective kappa opioid receptor antagonist, antagonized the attenuation of 5-HTP-induced HTR by tramadol. In conclusion, administration of tramadol systemically inhibits 5-HTP-induced HTR in mice by activating opiatergic system in the CNS. Our findings show that mu and kappa opioid receptors, but not delta opioid receptor, play an important role in the regulation of serotonergic function in the CNS.
authors.affiliation: National Institute on Drug Dependence, Peking University, Xue Yuan Road 38, Haidian District, Beijing 100083, PR China.
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Sun
authors.forename: Ji-Wang
authors.initials: JW
authors.lastname: Zheng
authors.forename: Keng
authors.initials: K
authors.lastname: Wang
authors.forename: Rui-Ke
authors.initials: RK
authors.lastname: Liu
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Liang
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000502:physiology; D014147:Tramadol / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014147:Tramadol; D009020:Morphine; D006916:5-Hydroxytryptophan