Evaluation of non-clinical anxiety disorder models / 药学学报

Anxiety disorders are one of the most common mental disorders in adults, the cause of which derives from a combination of genetics and environmental factors. A series of animal models have been established according to their pathogenesis to measure the level of anxiety or induce anxiety only, and these models have been widely applied in the non-clinical evaluation of anxiolytics. In this review, we present the current trends in the study of anxiety disorders and summarize typical non-clinical anxiety animal models, including models that both measure anxiety levels and induce anxiety, and models that induce anxiety only. This review summarizes the important issues in standardized non-clinical research of anxiety disorders and proposes criteria for the selection of an appropriate R&D model.

Exploration of nonclinical pharmacodynamics evaluation system of Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia among elderly people. The pathogenesis of AD is still unclear, and currently approved drugs only provide symptomatic benefits and do not prevent or delay progressive neurodegeneration. Meanwhile, potential drugs in development are facing great challenges in clinical translation. Therefore, finding effective treatment for the unmet clinical needs of AD is of great economic value and social significance. In this review, we will summarize the current models and pharmacodynamics evaluation methods of anti-AD drug based on the recent studies at home and abroad, and provide reference for drug development in AD at nonclinical stage.

Improvements of motor and cognitive functions in the rats with permanent middle cerebral artery occlusion treated with acupuncture and rota-rod training / 中国针灸

OBJECTIVE@#To explore the effects on the recovery of the motor and cognitive functions of the rats with permanent middle cerebral artery occlusion (pMCAO) after treated with 's three-needle acupuncture at head acupoints combined with rota-rod training.@*METHODS@#A total of 38 male SD rats were randomized into 3 groups, named a sham-operation group (11 rats), a model group (13 rats) and a treatment group (14 rats). The electrocoagulation method was adopted to establish the model of pMCAO on the right cerebrum. Starting from the 1st day after successful modeling, acupuncture was applied to the "three points of intelligence", the "three points of temporal area" and the "three points of brain". Additionally, the rota-rod training was used. Acupuncture was given once a day and the training was three times a day. In the sham-operation group and the model group, empty grasp fixation was performed when acupuncture was applied in the treatment group, and there was no intervention at the rest of the time. There was 1 day of interval after consecutive 6 days of intervention. Totally, the intervention was for 3 weeks. After modeling, the brain section was collected from 3 rats of each group on the 1st day and was stained with TTC to observe the condition of cerebral ischemia. From day 1 to 7, the neurological function score was evaluated. The footprint analysis and rota-rod test were performed on day 1, 7, 14 and 21. The Morris water maze test was performed from day 22 to 26.@*RESULTS@#Compared with the sham-operation group, cerebral ischemia presented obviously, the score of neurological function was increased, the back front distances on the left were increased on day 1, 7 and 14 separately, the revolutions per minute (RPM) of the rota-rod were reduced at each of the above 4 time points, the latency of navigation trial was increased and the movement time percentage in Q3 quadrant of spatial probe trial was reduced in the model group (0.05), the score of neurological function was reduced on day 6, the back front distance on the left was reduced on day 14, RPM of the rota-rod were increased on day 14 and 21, the latency of navigation trial were reduced from day 23 to 25 and the movement time percentage in Q3 quadrant of spatial probe trial was increased in the treatment group (<0.01, <0.05).@*CONCLUSION@#'s three-needle acupuncture at head acupoints combined with rota-rod training improve the behavioral performance of pMCAO rats and promote the recovery of motor and cognitive functions.

The effects of offspring's behavior and SERT and TPH during the lactation exposure to fluoxetine / 中国神经精神疾病杂志

Objective To explore the influence of the lactation exposure to fluoxetine on offspring's behavior and serotonin transporter (SERT) and tryptophan hydroxylase (TPH). Methods Six SD pregnant rats were randomly divided into 2 groups (n=3 each group). Experimental maternal rats were intraperitoneally injected with fluoxetine at a dose of 12 mg/kg from postnatal day 5 to 21. The control group were injected with the same amount of normal saline. In infancy, the offspring's weight, hair length, eye opening and auditory development were measured. The free suspension test and bur?ied food pellets test were applied to evaluate the offspring's behaviors. After postnatal day 21, all the offspring were wean. At early childhood (P35d) and adulthood (P75d), 6 offspring rats from each group were executed to examine SERT and TPH in the prefrontal cortex by immunohistochemistry. Results The offspring's weight of experimental group was significantly lower than control group (P<0.05). The sensitivity of auditory in experimental group was significantly higher than control group (P<0.01). The time of free suspension in experimental group significantly was decreased comparing to control group (P<0.01). The SERT and TPH in prefrontal cortex was significantly lower in experimental group than those in control group either at childhood (P35d) or at adulthood (P75d) (P<0.05). Conclusion Lactation exposure to fluoxetine re?sults in offspring's abnormal development and behaviors through down-regulation of SERT and TPH in the prefrontal cor?tex.

Effects of Wenjing Tongluo Formula on GFAP Level in Perpheral Neuropathy Rats / 中国中医药信息杂志

Objective To discuss the treatment action and mechanism of Wenjing Tongluo Formula on oxaliplatin-induced perpheral neurotoxicity in rats. Methods Intraperitoneal injection was used to inject oxaliplatin 4 mg/kg to establish oxaliplatin-induced peripheral neurotoxicity rat models. Female Wistar rats were randomly divided into normal group, model group, and TCM group. TCM group was given Wenjing Tongluo Formula to soak rats’ limbs and tails. Rats in the model group were soaked with deionized water for comparison. Rats in the normal group received intraperitoneal injection with 5%glucose. Algesia hypersensitivity and anaphylaxis were detected under the mechanical stimulation and temperature. Immunohistochemical method was used to detect the expression of GFAP in L4-L6 spinal dorsal horn of rats. Explore the level of GLT-1 in L4-L6 dorsal root ganglia by RT-PCR. Results Rats in model group showed obvious behavioral changes compared with normal group (P<0.05);Rats in the TCM group improved in behavioristics compared with model group (P<0.01);number of positive cells in GFAP of rats in the model group increased compared with normal group (P<0.05);the increase in the TCM group was not obvious. Compared with normal group, astrocytes in spinal dorsal horn of model group were enlarged, protuberances increased, became coarse, and GLT-1 mRNA is decreased (P<0.05, P<0.01). Compared with model group, active cells and protuberances in the TCM group decreased (P<0.01), GLT-1 mRNA is increased (P<0.01). Conclusion Wenjing Tongluo Formula can improve behavioral changes of model rats under temperature and mechanical stimulation, probably related to harmful signal transmission induced by inhibition of astrocyte in spinal dorsal horn.