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

Abstract

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: Li-En Wang, Xue-Qiong Zhang, Yan-Qi Yin, Yong-He Zhang
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 64 Issue 2 Pg. 277-82 (Feb 2012) ISSN: 2042-7158 [Electronic] England
• PMID: 22221104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Chemical References

• Aminopyridines
• Drugs, Chinese Herbal
• Flavonoids
• Piperazines
• Receptors, Presynaptic
• Serotonin Receptor Agonists
• Receptor, Serotonin, 5-HT1A
• 4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine
• spinosin
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Pentobarbital

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
• Administration, Oral
• Aminopyridines (pharmacology)
• Analysis of Variance
• Animals
• Drugs, Chinese Herbal (pharmacology)
• Flavonoids (pharmacology)
• Hypothermia (chemically induced)
• Male
• Mice
• Mice, Inbred ICR
• Pentobarbital (toxicity)
• Piperazines (pharmacology)
• Receptor, Serotonin, 5-HT1A (metabolism)
• Receptors, Presynaptic (drug effects)
• Reflex, Righting (drug effects)
• Serotonin Receptor Agonists (pharmacology)