Effect of haloperidol decanoate on the rat brain : (morphological and neurochemical study) (형태학적 그리고 신경생화학적 연구) = Haloperidol decaroate의 처치가 백서 뇌에 미치는 영향

다국어 초록 (Multilingual Abstract)

To search for the pathogenesis of tardive dyskinesia(TD), there have been many experimental studies using vacuous chewing movement(VCM) as an animal model of TD. The most probable hypothesis for TD suggested by those studies is that increased glutamate levels induced by neuroleptic treatment could cause a degeneration of striatal cells, most likely cholinergic neurons. However, most studies supportive for the above hypothesis have an important methodological flaw that they examined the whole neuroleptic-treated animals, not VCM(+) ones which is a real animal model of TD In the present study, therefore, we first rated VCM scores and VCM(+) incidence (the criterion of VCM score for VCM(+) was 6 or more) in 3 control and 3 haloperidol groups which received respectively 3 different treatment schedules of vehicle of haloperidol decanoate: 4, 7 or 9 times' injections of vehicle or haloperidol decanoate were administered with each injection given every 3 weeks. After that, 3 VCM(+) groups were selected from each 3 haloperidol group and then VCM(+) and control rats were only sacrificed for further histological and neurochemical study. In the results of VCM scores and VCM incidence, we found that as treatment becomes longer, the increase of its scores and incidence was noted. For histological and neurochemical study, significant reuctions of density of medium-sized neurons and GABA levels were found in the striatum of VCM(+) group 3, compared to either its control group or other VCM(+) groups
Key Words. Haloperidol decanoate - Rat striatum - GABAnergic neurons - Glutamate - GABA
The incidence of tardive dyskinesia(TD) is 20-40% of patients(Khot et al. 1992)
treated chronically with typical antipsychotics. However, there is still no satisfactory management for it. To prevent the occurrence and develop an effective treatment of it, it is essential to explore the exact pathogenesis For that purpose, there have been many experimental researches using vacuous chewing movement(VCM) induced by a long-term administration of antipsychotic as a model of TD(Waddington 1990). One of the recent attracting hypotheses for TD suggested by those studies is a glutamate excitotoxicity hypothesis(Gunne and Andren 1993): chronic use of antipsychotic induce hyperglutamatergic state in basal ganglia which in turn could be neurotoxic and cause neuronal degeneration in that area. Even though glutamate excitotoxicity hypothesis is gaining more recognition nowadays, it should be mentioned that there are also many inconsistent results related to that. Most of the reasons for the inconsistency stem from different study designs in terms of drug dose, duration and route of administration, conditions fo experimental animals and etc. Above all, however, an important methodological flaw most of the studies(Gunne and Haggstrom 1983; Mithani et al, 1987; Rupniak et al 1987) have in common is that glutamate change was examined while regarding neuroleptic treated rats as a homogeneous group even though VCM(+) rats could be different from VCM(-) ones in terms of their glutamate responses to the neuroleptic treatment. Therefore, it is very important to examine abnormal findings specific only to the VCM(+) rats and compare them to the control. With an implementation of it, our study had three-fold purposes First, the incidences of VCM(+) groups VCM(+) group 1, 2 and 3, were obtained respectively from three haloperidol groups haloperidol group 1, 2 and 3 which received different treatment schedules of haloperidol decanoate Secondly, histological differences of the striatum between VCM(+) groups and control groups were examined.
Finally, tissue glutamate and GABA levels in the striatum of VCM(+) groups and control groups were measured and compared

목차 (Table of Contents)

• ABSTRACT
• 1.INTRODUCTION
• 2.MATERIALS AND METHODS
• 3.RESULTS
• 4.DISCUSSION
• 5.REFERENCES