The effect of fluid percussion injury of cerebral cortex on nicotine-inducedconditioned place preference in rats
| Autor: | CHEN, CHAO-HUNG, 陳昭宏 |
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| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 Traumatic brain injury (TBI) has been proved to cause a number of health problems which is not only functionally connected with the direct site of trauma, but also impacts the remote sites of the brain to lead to defects. In our previous study using the model of fluid percussion injury (FPI), we demonstrated that TBI suppresses dopamine release and reuptake and affects the metabolic rate and release probability of dopamine on the side of nigrostriatal system both ipsilateral and contralateral to the injury during both the acute and subacute stages after the injury. Thus, we predict this impact by TBI may also occur on the mesolimbicmesocortical dopaminergic neural pathway. In literatures, the increase of tobacco abuse was often observed in patients underwent TBI. Either in tobacco addicts or naïve patients to tobacco, the quantity of usage and liability to tobacco dependence would be both augmented. This suggests that the well-known activation of mesolimbic-mesocortical dopaminergic pathway, the common reward pathway, by chronic nicotine treatment may be affected by TBI. In the present study, we attempted to provide the biological evidence of this phenomenon by using animal behavioral models and neurochemical analyses. Using conditioned place preference (CPP) tests of nicotine, we found the loss of nicotine-induced CPP in rats with FPI (6 psi) on cortex, which was at the same dose of nicotine conditioning (0.4 mg/kg, s.c.) that was sufficient to induce CPP in control rats. Our results of fast scan cyclic voltammetry (FSCV) supports this behavioral finding by showing the lower releasing probability of dopamine at the shell of nucleus accumbens (NAcc). In high performance liquid chromatography (HPLC) analysis on dopamine content at the NAcc, there was no significant change caused by FPI, indicating the synthesis and package of dopamine in vesicles may not be affected. In order to investigate TBI-induced augmentation of nicotine abuse in addicts, we also used the rat pre-exposed to chronic nicotine, and then subjected to FPI and following CPP tests. However, the data showed that nicotine pre-treatment could completely abolish nicotine-induced CPP in both control and FPI rat. This implied a possible desensitization/tolerance to nicotine reward even after a period of withdrawal. Furthermore, we examined the possible impact of TBI on the severity of nicotine abstinence syndromes, although it is with less connection with the dopaminergic system. Our results revealed no difference of the severity of syndromes between those of control and FPI rats. This could partially rule out the effects of TBI on the negative reinforcement of withdrawal to drive the continuous use of nicotine in prevention of those syndromes. Overall, our results from neurochemical and behavioral studies were generally consistent. Our findings validate the impacts of TBI to affect mesolimbic-mesocortical dopaminergic pathway, thereby to reduce nicotine-induce reward. Therefore, the higher stimulation by nicotine could be required to obtain the sufficient level of dopamine to acquire the sensation of the same extent of reward. That can be referred to the increase of tobacco abuse in TBI patients in clinics. However, many other factors affected by TBI should be also considered and further investigated, because the dopaminergic system is not the only neural substrate of reward in brain. For example, the serotoninergic and adrenergic systems could be also involved. Nevertheless, our present study demonstrated a clear impact of TBI on mesolimbic-mesocortical dopaminergic pathway to reduce dopamine releasing probability at the shell of NAcc, which implied a connection of reduced reward of nicotine shown in the animal behavioral experiments. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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