Augmentative effect of spinosin on pentobarbital-induced loss of righting reflex in mice associated with presynaptic 5-HT1A receptor

Objectives This study investigated whether spinosin potentiates pentobarbital-induced loss of righting reflex (LORR) in mice via 5-HT1A 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-HT1A 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-HT1A 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-HT1A autoreceptors in mice. Conclusions Based on our previous results and the present data, it should be presumed that presynaptic 5-HT1A 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.