Anxiolytic-like effect of central administration of NOP receptor antagonist UFP-101 in rats submitted to the elevated T-maze

Marcelo Duzzioni, Filipe S.Duarte, Leandro R. Leme, Elaine C.Gavioli, Thereza C.M. De Lima

Abstract

Depression and anxiety disorders present several genetic and neurobiological similarities. Drugs with antidepressant activity are effective in the treatment of a wide spectrum of anxiety disorders. Preclinical results showed that acute and chronic treatment with the NOP antagonist [Nphe¹,Arg¹⁴,Lys¹⁵]N/OFQ-NH₂ (UFP-101) produced antidepressant-like effects in rodents. Thus, the present study aimed to investigate the effect of central administration of UFP-101 on the anxiety-related behavior in rats as evaluated in the elevated T-maze (ETM) test. Our results showed that UFP-101 reduced the latency of inhibitory avoidance in the ETM, indicating an anxiolytic-like effect. The endogenous peptide N/OFQ prevented this anxiolytic-like action of UFP-101, demonstrating its modulation via central NOP receptors. However, UFP-101 failed to interfere with the latency to escape. No change was observed in locomotor activity after UFP-101 treatment, ruling out any nonspecific motor effect. In conclusion, our results showed that the central administration of UFP-101 presents an anxiolytic-like effect in rats evaluated in the ETM test, providing new insights for drug development to treat anxiety disorders targeting the N/OFQ-NOP receptor system.

Highlights

► The putative anxiolytic-like effect of UFP-101, a NOP antagonist was ► investigated. ► UFP-101 showed an anxiolytic-like profile of action in the ETM. ► This effect was prevented by pretreatment with N/OFQ, the NOP agonist. ► Locomotor activity was not changed by UFP-101.

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