Nakahara T, Matsumoto T, Hirano M, Uchimura H, Yokoo H, Nakamura K, Ishibashi K, Hirano H
Peptides. 1985 Nov-Dec;6(6):1093-9. doi: 10.1016/0196-9781(85)90433-4.
Acute and chronic effects of gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide (DN-1417) were investigated on motor activity, dopamine (DA) metabolites and DA receptors in various brain regions of rats. The motor activity, as measured with Automex recorder, was enhanced after a single injection with DN-1417 (20 mg/kg, IP), and the motor stimulating action persisted during 21 daily injections. Acute DN-1417 elevated both homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in 7 brain regions, prefrontal cortex polar, medial and lateral fields, nucleus accumbens, olfactory tubercles, amygdala and striatum. After chronic treatment for 7 days, the acute effect of DN-1417 on DA metabolites disappeared in all regions except for the striatum in which DN-1417 still increased HVA and DOPAC. The response of striatal DA metabolites was also observed after chronic treatment for 21 days. Chronic DN-1417 produced no significant change in 3H-spiperone binding in the prefrontal cortex, nucleus accumbens, olfactory tubercles and striatum, while striatal 3H-DA binding displaced by 30 nM spiperone was enhanced after chronic treatment. These results indicate that DN-1417 interacts with mesocortical, mesolimbic and nigrostriatal DA systems in the different modes of action. The lack of tolerance to motor hyperactivity, however, raises the question as to whether DN-1417-induced hyperactivity may be mediated by the activation of mesolimbic DA neurons. The involvement of nigrostriatal neurons in DN-1417-induced motor hyperactivity is suggested.
研究了γ-丁内酯-γ-羰基-组氨酰-脯氨酰胺（DN-1417）对大鼠不同脑区运动活性、多巴胺（DA）代谢产物及DA受体的急性和慢性影响。用Automex记录仪测量，单次腹腔注射DN-1417（20mg/kg）后运动活性增强，且在21天每日注射期间运动刺激作用持续存在。急性给予DN-1417可使7个脑区（前额叶皮质极区、内侧和外侧区、伏隔核、嗅结节、杏仁核和纹状体）的高香草酸（HVA）和3,4-二羟基苯乙酸（DOPAC）水平均升高。慢性治疗7天后，DN-1417对DA代谢产物的急性作用在除纹状体以外的所有区域均消失，而在纹状体中DN-1417仍可升高HVA和DOPAC。慢性治疗21天后也观察到了纹状体DA代谢产物的反应。慢性给予DN-1417对前额叶皮质、伏隔核、嗅结节和纹状体中3H-司哌酮结合无显著影响，而慢性治疗后，30nM司哌酮置换的纹状体3H-DA结合增强。这些结果表明，DN-1417以不同作用方式与中脑皮质、中脑边缘和黑质纹状体DA系统相互作用。然而，对运动亢进缺乏耐受性引发了一个问题，即DN-1417诱导的多动是否可能由中脑边缘DA神经元的激活介导。提示黑质纹状体神经元参与了DN-1417诱导的运动亢进。
