Korean J Physiol Pharmacol.  2018 Mar;22(2):183-192. 10.4196/kjpp.2018.22.2.183.

Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder

• Lee B
• Shim I
• Lee H
• Hahm DH

• KMID: 2410108
• DOI: http://doi.org/10.4196/kjpp.2018.22.2.183

Abstract

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

Keyword

Anxiety; Berberine; Dopamine; Post-traumatic stress disorder; Single prolonged stress

MeSH Terms

Animals
Anxiety*
Arm
Berberine*
Depression
Dopamine*
Grooming
Hippocampus
Humans
Rats*
RNA, Messenger
Stress Disorders, Post-Traumatic*
Tyrosine 3-Monooxygenase
Vesicular Monoamine Transport Proteins
Berberine
Dopamine
RNA, Messenger
Tyrosine 3-Monooxygenase
Vesicular Monoamine Transport Proteins

Figure

• 

  Fig. 1 Experimental schedule for developing single prolonged stress (SPS)-induced anxiety-like behaviors, and berberine (BER) treatment in rats Separate groups of rats (n=6 or 7 animals per group) were used for all experiments.

• 

  Fig. 2 Effects of BER administration on the percentage of time spent in the open and closed arms, numbers of entries into the open and closed arms, anxiety index, unprotected head dips, and grooming behavior on the elevated plus maze (EPM) test of rats exposed to SPS. *p<0.05, **p<0.01 vs. SAL group; #p<0.05, ##p<0.01 vs. PTSD group.

• 

  Fig. 3 Effects of BER administration on locomotion and exploratory behavior in the open filed test (OFT) of rats exposed to SPS. Change in the number of crossing in the central zone and the time spent in the central and peripheral zones. *p<0.05, **p<0.01 vs. SAL group; #p<0.05, ##p<0.01 vs. PTSD group.

• 

  Fig. 4 Effects of BER on dopamine (DA) concentration in the brains of rats exposed to SPS for 14 consecutive days. *p<0.05, **p<0.01 vs. SAL group; #p<0.05 vs. PTSD group.

• 

  Fig. 5 Effects of BER administration on expression of tyrosine hydroxylase (TH), DA transporter (DAT), and vesicular monoamine transporter-2 (VMAT-2) mRNA in rats during SPS-induced anxiety symptoms. Polymerase chain reaction bands on agarose gel and their relative intensities are indicated. The expression levels of TH, DAT, and VMAT-2 mRNA were normalized to that of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA as an internal control. *p<0.05, **p<0.01 vs. the SAL group, #p<0.05, ##p<0.01 vs. the PTSD group.

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