Dopamine(DA) Antagonists Modulate Methamphetamine(MAP)-induced Behavioral Sensitization in Rats

• Main Authors: Cheng, Hui-Chi, 鄭惠及
• Other Authors: Shaw, Kai-Ping
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/84751387230920013604

碩士 === 國防醫學院 === 生物及解剖學研究所 === 87 === Abstract Methamphetamine(MAP), a potent Central Nerve System stimulant, is currently considered the major illicit drug in Taiwan. Repeated administrations of MAP followed with MAP challenged after period of remission results in an augmentation of its locomotion and/or stereotyped behavior, a phenomenon known as behavioral sensitization. In humans, chronic psychostimulant abuse led to an increase in anxiety and paranoia that are indistinguishable from paranoid schizophrenia. Thus, behavioral sensitization induced by MAP could be attributed to a direct pharmacological action of dopamine (DA) receptors. It suggests that long-term enhancement of MAP-induced dopamine releasing in the striatum and expression of schizophrenic symptoms may reflect the development of dissociation between pre-synaptic as well as post-synaptic DA receptor stimulation. The purposes of this study are: (1) to observe and analyze the stereotypy and behavioral change subsequent to MAP-induced behavioral sensitization in rats, (2) to distinguish the different quantities of various locomotion and stereotypy of MAP-challenged sensitization by Digiscan Optical Animal Activity Monitoring System, (3) to elucidate the mechanisms of MAP-induced toxicity by using behavioral assessment, and (4) to clarify the possible therapeutic effect of DA antagonists that modulate the behavioral sensitization. A model of behavioral sensitization after chronic self-administration of MAP(0.05 mg/ml) in rats is applied to this study. We established four groups including chronically MAP self-administration for one month as chronic MAP rats. In addition to control and chronic MAP rats, pretreated with dopamine antagonist including haloperidol(1.5mg/kg, i.p.) as haloperidol rats and chlorpromazine(25mg/kg, i.p.) as chlorpromazine rats. On the day of behavioral assessment, a 60 minute''s period of accommodation, followed with monitoring of locomotion activity and stereotyped behaviors after MAP challenged (3 mg/kg, i.p.). The results demonstrate (1) repeated MAP challenged in chronic MAP rats can induced behavioral sensitization, (2) pretreated of haloperidol and chlorpromazine can modulate behavioral sensitization, and (3) behavioral sensitization of never system is D2 receptor-specific. In conclude, these results demonstrate that chronic self-administration rats are eligible to study antagonist’s effect of DA system in the MAP-induced behavioral sensitization. Further more, these experiments support the mechanisms of DA D2 antagonists such as haloperidol and chlorpromazine can restore the MAP-induced behavioral sensitization in rats that may be potential for therapy of MAP-induced toxicity accompanied with psychosis in MAP abusers.