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


RESULTS
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.
Department of Pharmacology, School of Basic Medical Science, Peking University, Beijing, China.
Li-En
LE
Wang
Xue-Qiong
XQ
Zhang
Yan-Qi
YQ
Yin
Yong-He
YH
Zhang
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000284:Administration, Oral; D000631:Aminopyridines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010424:Pentobarbital / Q000633:toxicity*; D010879:Piperazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects*; D057897:Reflex, Righting / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000631:Aminopyridines; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D010879:Piperazines; D017661:Receptors, Presynaptic; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; C055669:spinosin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010424:Pentobarbital