OBJECTIVES: This study investigated whether spinosin potentiates pentobarbital-induced loss of righting reflex (LORR) in mice via 5-HT(1A) receptors. METHODS: Our primary endpoint for sedation was LORR. In addition, the basal rectal temperature was measured. KEY FINDINGS: The results demonstrated that the 5-HT(1A) agonist 8-OH-DPAT (s.c.) induced reductions in duration of LORR at 0.1, 0.5 and 1.0 mg/kg (P < 0.01), and prolongation of LORR latency at 0.5 and 1.0 mg/kg (s.c., P < 0.01) in pentobarbital (45 mg/kg, i.p.)-treated mice. This effect of 8-OH-DPAT was antagonized either by 5-HT(1A) antagonist p-MPPI (5 mg/kg, i.p.) or by spinosin (15 mg/kg, i.g.) with significance, respectively. Co-administration of spinosin and p-MPPI both at ineffective doses (spinosin at 5.0 mg/kg, i.g. and p-MPPI at 1.0 mg/kg, i.p.) showed significant augmentative effects in reducing latency to LORR, and increasing LORR duration (P < 0.01) in pentobarbital-treated mice. On the other hand, spinosin inhibited 8-OH-DPAT-induced hypothermia, which has been generally attributed to the activation of somatodendritic 5-HT(1A) autoreceptors in mice. CONCLUSIONS: Based on our previous results and the present data, it should be presumed that presynaptic 5-HT(1A) autoreceptor mechanisms may be involved in the inhibitory effect of spinosin on 8-OH-DPAT-induced hypothermia and also in the potentiating effect of spinosin on pentobarbital-induced LORR in mice.
OBJECTIVES: This study investigated whether spinosin potentiates pentobarbital-induced loss of righting reflex (LORR) in mice via 5-HT(1A) receptors. METHODS: Our primary endpoint for sedation was LORR. In addition, the basal rectal temperature was measured. KEY FINDINGS: The results demonstrated that the 5-HT(1A) agonist 8-OH-DPAT (s.c.) induced reductions in duration of LORR at 0.1, 0.5 and 1.0 mg/kg (P < 0.01), and prolongation of LORR latency at 0.5 and 1.0 mg/kg (s.c., P < 0.01) in pentobarbital (45 mg/kg, i.p.)-treated mice. This effect of 8-OH-DPAT was antagonized either by 5-HT(1A) antagonist p-MPPI (5 mg/kg, i.p.) or by spinosin (15 mg/kg, i.g.) with significance, respectively. Co-administration of spinosin and p-MPPI both at ineffective doses (spinosin at 5.0 mg/kg, i.g. and p-MPPI at 1.0 mg/kg, i.p.) showed significant augmentative effects in reducing latency to LORR, and increasing LORR duration (P < 0.01) in pentobarbital-treated mice. On the other hand, spinosin inhibited 8-OH-DPAT-induced hypothermia, which has been generally attributed to the activation of somatodendritic 5-HT(1A) autoreceptors in mice. CONCLUSIONS: Based on our previous results and the present data, it should be presumed that presynaptic 5-HT(1A) autoreceptor mechanisms may be involved in the inhibitory effect of spinosin on 8-OH-DPAT-induced hypothermia and also in the potentiating effect of spinosin on pentobarbital-induced LORR in mice.
Authors: Sang Yoon Ko; Hyung Eun Lee; Se Jin Park; Se Jin Jeon; Boseong Kim; Qingtao Gao; Dae Sik Jang; Jong Hoon Ryu Journal: Biomol Ther (Seoul) Date: 2015-03-01 Impact factor: 4.634
Authors: Elena M Kondaurova; Alexandra V Plyusnina; Tatiana V Ilchibaeva; Dmitry V Eremin; Alexander Ya Rodnyy; Yulia D Grygoreva; Vladimir S Naumenko Journal: Int J Mol Sci Date: 2021-12-11 Impact factor: 5.923