Korean J Physiol Pharmacol.  2014 Jun;18(3):191-200. 10.4196/kjpp.2014.18.3.191.

Alpha-Asarone, a Major Component of Acorus gramineus, Attenuates Corticosterone-Induced Anxiety-Like Behaviours via Modulating TrkB Signaling Process

• Lee B
• Sur B
• Yeom M
• Shim I
• Lee H
• Hahm DH

• KMID: 2285510
• DOI: http://doi.org/10.4196/kjpp.2014.18.3.191

Abstract

We investigated the anxiolytic-like activity of alpha-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

Keyword

Anxiety; Brain-derived neurotrophic factor; Corticosterone; Tyrosine hydroxylase; alpha-asarone

MeSH Terms

Acorus*
Animals
Anti-Anxiety Agents
Anxiety
Axis, Cervical Vertebra
Brain-Derived Neurotrophic Factor
Corticosterone
Head
Hippocampus
Humans
Hypothalamus
Locus Coeruleus
Male
Models, Animal
Rats
Receptor, trkB
RNA, Messenger
Tyrosine 3-Monooxygenase
Anti-Anxiety Agents
Brain-Derived Neurotrophic Factor
Corticosterone
RNA, Messenger
Receptor, trkB
Tyrosine 3-Monooxygenase

Figure

• 

  Fig. 1 Effect of AAS administration on body weights gain (A) and blood levels of corticosterone (B) of the rats under chronic CORT injection for 21 consecutive days. *p<0.05, **p<0.01 vs. SAL group; #p<0.05 vs. CORT group.

• 

  Fig. 2 The percentage of time spent on open arm (A) and the numbers of entries into open and closed arms (B) in the elevated plus maze after repeated CORT administration. Their behavior was recorded for 5 min at 7, 14, and 21 days following repeated CORT administration. Effect of AAS administration on the percentage of time spent on open arm (C) and the numbers of entries into open and closed arms (D) in the elevated plus maze, the time spent of head dipping (E) and the numbers of head dipping (F) in the hole board test, and activity counts of locomotor activity and total number of line crossing in the open-field test (G) during chronic CORT injection *p<0.05, **p<0.01 vs. SAL group; #p<0.05 vs. CORT group.

• 

  Fig. 3 Effect of AAS administration on the mean number of corticotrophin-releasing factor (CRF) expression in the paraventricular nucleus (PVN) of the hypothalamus and tyrosine hydroxylase (TH) expression in the locus coeruleus (LC). Representative photographs and the relative percentage values are indicated in (A). Effect of AAS administration on the expression of (BDNF) and TrkB mRNAs in rats subjected to chronic CORT injection for 21 consecutive days. PCR bands on agarose gel and their relative intensities are indicated in (B). *p<0.05, **p<0.01 vs. the SAL group; #p<0.05 vs. CORT group.

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