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

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.

Systemic Administration of Curcumin Affect Anxiety‐Related Behaviors in a Rat Model of Posttraumatic Stress Disorder via Activation of Serotonergic Systems

“…Some studies suggested that Elettaria cardamomum methanolic extract significantly recovered anxiety-like behaviors in a rat model of PTSD conducted by the OFT, EPM, and rotarod tests [ 38 ]. Also, administering berberine, an isoquinoline alkaloid derived from Korean traditional medicinal herbs, such as Coptidis Rhizoma after SPS procedure, significantly increased the time spent in the open arms in the EPM and prevented reduction in brain level of dopamine [ 39 ]. Therefore, herb-derived compounds could lead to the development of novel therapeutics for treating PTSD.…”

Biologically active isoquinoline alkaloids covering 2014–2018

“…Depression is the most common mental disorder in humans. Berberine upregulated BDNF expression in the hippocampus to lessen corticosterone‐induced depressive‐like behavior in mice 322 and enhanced dopamine expression to alleviate symptoms of anxiety in rats with posttraumatic stress disorder 323 . It also exerted antidepressant‐like effects in ovariectomized mice and decreased immobility time in a dose‐dependent manner.…”

“…Lycorine-type alkaloids, including lycorine(321), acetycaranine(322), caranine(323), galanthine(324), 9-Odemethylgalanthine (325), as well as α-crinane types, haemanthamine (326), haemanthidine (327), and β-crinane types, ambelline (328), 11-O-acetylambelline (329), 1-O-acetylbulbisine (330), undulatine (331), crinamidine (332), buphanamine (333), and srinine (334), were isolated from Zephyranthes robusta, Chlidanthus fragrans, Nerine bowdenii, and Narcissus poeticus cv. Brackenhurst by Cahlíková and collegaues, these compounds show moderate F I G U R E 15 The chemical structures of compounds 299−320 SHANG ET AL.…”

Berberine Facilitates Extinction and Prevents the Return of Fear

“…Berberine, an OTC medication in China, has been verified well for safety in clinical trials (Gupte, 1975). Besides, previous studies have shown that berberine affected the DA and N-methyl-D-aspartate (NMDA) systems, which is the molecular mechanism of cognitive enhancers (Yoo et al, 2006;Kaplan and Moore, 2011;Kawano et al, 2015;Lee et al, 2018). Shen et al (2020) demonstrated that extinction training combined with berberine treatment facilitated the extinction of drug memory.…”

“…Moreover, berberine modulates oxytocin receptors to attenuate methamphetamine consumption and anxiety-like behaviors (Alavijeh et al, 2019). Furthermore, berberine has been reported to alleviate anxiety-like behavior in rats with posttraumatic stress disorder and facilitate extinction of drug memories (Lee et al, 2018;Shen et al, 2020). In Shen and colleagues' study, they found that brain-derived neurotropic factor (BDNF) and AMPA receptors (GluA1 and GluA2) were associated with enhanced extinction memory consolidation (Shen et al, 2020).…”