• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.5
• /
• pp.525-538
• /
• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

• Science of Emotion and Sensibility
• /
• v.20 no.4
• /
• pp.113-126
• /
• 2017

The purpose of the study was to find grey matter (GM) and white matter (WM) volume reduction in the brain reward system among patients with alcohol dependency. This study investigated regional GM and WM in chronic alcoholic patients, focusing primarily on the reward system, including principal components of the mesocorticolimbic reward circuit as well as cortical areas with modulating and oversight functions. Sixteen abstinent long-term chronic alcoholic men and demographically matched 16 healthy control men participated in the study. Morphometric analysis was performed on magnetic resonance brain scans using voxel-based morphometry (VBM)-diffeomorphic Anatomical Registration through Exponentiated Liealgebra (DARTEL). We derived GM and WM volumes from total brain and cortical and subcortical reward-related structures. Morphometric analyses that revealed the total volume of GM and WM was reduced and cerebrospinal fluid (CSF) was increased in the alcohol group compared to control group. The pronounced volume reduction in the reward system was observed in the GM and WM of the nucleus accumbens (NAc), GM of the amygdala, GM and WM of the hippocampus, WM of the thalamus, GM and WM of the insula, GM of the dorsolateral prefrontal cortex (DLPFC), GM of the orbitofrontal cortex (OFC), GM of the cingulate cortex (CC), GM and WM of the parahippocampal gyrus in the alcohol group. We identified volume reductions in WM as well as GM of reward system in the patients with alcohol dependency. These structural deficits in the reward system elucidate underlying impairment in the emotional and cognitive processing in alcoholism.