Tramadol reduces the 5-HTP-induced head–twitch response in mice via the activation of μ and κ 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 δ opioid receptor antagonist NTI, β-FNA, a selective μ opioid receptor antagonist, and nor-BNI, a selective κ 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 μ and κ opioid receptors, but not δ opioid receptor, play an important role in the regulation of serotonergic function in the CNS.