Effects of tetrahydropalmatine on post-traumatic stress disorder-induced changes in rat brain gene expression

Abstract

The aim of this research proposal was to investigate the effects of tetrahydropalmatine (THP) on gene expression in a post-traumatic stress disorder (PTSD) rodent model. Eighty male Sprague-Dawley rats were randomly assigned to the nonstressed groups or the 3-day restraint shock PTSD rodent model groups. There were four groups within the nonstressed rats (control, THP, midazolam, and midazolam with THP) and four groups within the stressed rats (control, THP, midazolam, and midazolam with THP). After injection the subjects were euthanized and the amygdala and hippocampus were sent for reverse transcriptase-polymerase chain reaction gene expression analysis. Of the genes interrogated, 17 genes in the amygdala and 18 genes in the hippocampus were found to have significant changes in gene expression and regulation. Significant transcriptional fold changes were found in important genes involved in dopamine, serotonin, acetylcholine, and gamma-aminobutyric acid neurotransmitter systems. The results provide quantifiable data demonstrating gene expression changes in PTSD-stressed and nonstressed rats receiving various treatments. These findings contribute important data to the limited molecular details pertaining to the neurobiology of PTSD.

L-Tetrahydropalmatine Ameliorates Development of Anxiety and Depression-Related Symptoms Induced by Single Prolonged Stress in Rats

“…In other time periods, all animals had free access to food. The standard doses of THP in the rat and considering the long-term treatment used in the present study was based on previous study (Ceremuga et al ., 2013). THP (10, 20, 50 mg/kg body weight, Sigma-Aldrich Chemical Co. St. Louise, MO, USA) and the positive drug fluoxetine (15 mg/kg, FLX, Fluoxetine hydrochloride; Eli Lilly and Company, Basingstoke, Hampshire) were administered by intraperitoneally (i.p.)…”

“…Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric or psychological disorder that develops in a subset of individuals following severe, life-threatening traumatic stress (Ceremuqa et al ., 2013). It is characterized by intrusive recollections of the traumatic event, avoidance of reminders of the event, hyperarousal, and as being outside the realm of a normal human experience (Serova et al ., 2014).…”

“…(Ceremuga et al ., 2013). This compound improves multiple physiological symptoms and produces a variety of biological effects in the central nervous and immune systems.…”

“…Several studies have shown that THP significantly inhibits cocaine or methamphetamine-induced locomotor activity and activation of extracellular-regulated kinase (ERK) in the nucleus accumbens (NAc) and caudate putamen (CPu) of mice (Zhao et al ., 2014), as well as the cocaine-enhanced locomotor activity and changes in extracellular dopamine (DA) in the NAc of rats (Xi et al ., 2007). Additionally, THP has been reported to attenuate PTSD-induced changes in gene expression, such as those involving DA, serotonin, and acetylcholine, in the amygdala and hippocampus of rats (Ceremuga et al ., 2013). …”

Effects of Tetrahydropalmatine (THP) on PTSD-induced Changes in Rat Neurobehavior

“…Recently, our lab demonstrated a significant anxiolytic effect and decrement in motor movements with the administration of tetrahydropalmatine (THP), a component isolated from C. yanhusuo in the laboratory rat (Henkes et al, 2011). Currently, gene expression changes have been shown in dopamine, serotonin, acetylcholine, and gammaaminobutyric acid neurotransmitter systems when THP was administered in a PTSD rodent model (Ceremuga et al, 2013). Although there is evidence of central nervous system modulation, there are no studies evaluating the potential therapeutic properties of THP or C. yanhusuo in PTSD.…”