Study on the Influences of Long-Term Ritalin Medication on Rat Nervous System

• Main Authors: TAO-YUAN WNAG, 王道淵
• Other Authors: Yu-Show Fu
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/3mc52q

碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 103 === Attention Deficit Hyperactivity Disorder (ADHD) is a disorder that having about 7.5 % prevalence in Taiwanese children. People who have ADHD usually take medicals to retard symptoms from the age of elementary school to college, may be through adulthood. Since the ethology of ADHD is still not clear, researchers found that exceeded dopamine transporter activity and, blunted dopamine receptor may result in dopamine system dysfunction, perhaps, lead to ADHD. Consequently, the effects of long term medication in ADHD drugs come into a non-neglectable issue. Methylphenidate, trade name: Ritalin, is one of the most common, widely used in clinical, as well as less side effects. By blocking dopamine transporter, methylphenidate reduce dopamine reuptake, and increase dopamine concentration in synaptic cleft. However, weather methylphenidate affect adolescent nerve system or not, is still undiscovered. Therefore, we have interest in the effects of long term medication of MPH on rats. From the age of one month, rats were treated with methylphenidate solution by a gavage tube twice a day for 7 months. The rats were sacrificed 14 days after the last time treatment of methylphenidate. Rats were divided into three groups on the basis of different treatments. The first one is Normal group; the rats received 3% sucrose solution. The second group is Low -dose group; the rats were treated with methylphenidate at a dose of 2mg/kg/twice a day. The third group is High-dose group; the rats were treated with methylphenidate at a dose of 10mg/kg/ twice a day. In order to investigate whether treatment of methylphenidate would affect body weight, rats were weighted every 14 days. The results indicated that the average body weight decreased significantly in the rats of High-dose group from the age at 4 months to 8.5 months after administration (P<0.05). In open field test, the total traveled distance and time within 30 minutes were quantified every 14 days. During the period of methylphenidate medication, neither the travel distance nor the travel time different between three groups. However, after 14 days withdraw, we found that the locomotion rebounded in the rats of High-dose group and Low-dose group, both travel distance and time have significant higher than rats in the Normal group. The immunostaining to count the number of dopaminergic neurons in substantia nigra, serotonin neurons in dorsal raphe nucleus, and cholinergic neurons in tegmental nucleus, the results revealed the number of immunostaining marked cells in those area increased after 7 months methylphenidate administration and 14 days withdraw. Furthermore, whole cell clamp to quantify the alterations of membrane property of dopaminergic cells. After recording, we sorted dopaminergic neurons by firing frequency 10Hz, and proportion of high firing frequency cells reduced in High-dose group at 8.5 months old. We also found that spike amplitude increased in High-dose group. In our research, we found that long-tern methylphenidate medication probably decline dopaminergic neurons, and increase locomotion, and alter proportion of dopaminergic neurons. Thus, we hypothesize, once methylphenidate has ceased after a long-tern treatment, rats might develop ADHD-like behavior and pathology. We believe those results gained from this study will be helpful in the comprehension of mechanism and confluence of methylphenidate.