Ericson E, Ahlenius S
Department of Pharmacology, Astra Arcus, SE-151 85, Södertälje, Sweden.
Brain Res. 1999 Mar 20;822(1-2):200-9. doi: 10.1016/s0006-8993(99)01144-0.
The objective was to examine effects of galaninrat on forebrain monoamine synthesis and on spontaneous locomotor activity in the rat. The rate of monoamine synthesis was estimated by measuring the accumulation of l-DOPA and 5-HTP, following inhibition of cerebral aromatic l-amino acid decarboxylase by means of NSD-1015 (100 mg kg-1 i.p.), after i.c.v. or intracerebral administration of galanin in adult male Wistar rats. Spontaneous locomotor activity was observed in an automated open-field arena ( approximately 0.5 m2). The i.c.v. administration of galanin (0.5-5.0 nmol bilaterally) produced a dose-dependent, statistically significant, increase in DOPA accumulation throughout the neostriatum, and in the olfactory bulb, indicating an increase in the rate of DA synthesis. No increase was observed in brain areas where noradrenaline is the predominant catecholamine, such as the neocortex or the ventral hippocampus. In addition, there was a tendency for an increase in 5-HTP accumulation in the dorso-lateral neostriatum and in the accumbens. The same i.c.v. administration of galanin produced a dose-dependent, and statistically significant, decrease in spontaneous locomotor activity. The effect on forebrain DA synthesis could also be produced by local bilateral application of galanin (2x1 nmol) into the ventral tegmental area, but not the nucleus accumbens (2x2 nmol). There were no effects on forebrain DOPA or 5-HTP accumulation by the local application of galanin into the locus coeruleus, or into the dorsal raphe nucleus. It is concluded that the neuropeptide galanin modulates forebrain dopaminergic neurotransmission. The effect appears to be mediated at the somato-dendritic level of the meso-neostriatal pathway, and could perhaps be utilized to normalize perturbations ascribed to dysfunction in this neuronal pathway, such as schizophrenia.
目的是研究甘丙肽对大鼠前脑单胺合成及自发运动活性的影响。在成年雄性Wistar大鼠经脑室内（i.c.v.）或脑内注射甘丙肽后，通过NSD - 1015（100 mg kg-1腹腔注射）抑制脑芳香族L - 氨基酸脱羧酶，然后测量L - DOPA和5 - HTP的积累来估算单胺合成速率。在一个自动旷场 arena（约0.5平方米）中观察自发运动活性。脑室内注射甘丙肽（双侧0.5 - 5.0 nmol）使整个新纹状体及嗅球中DOPA积累呈剂量依赖性且具有统计学意义的增加，表明多巴胺合成速率增加。在以去甲肾上腺素为主要儿茶酚胺的脑区，如 neocortex 或腹侧海马体中未观察到增加。此外，在背外侧新纹状体和伏隔核中5 - HTP积累有增加趋势。相同的脑室内注射甘丙肽使自发运动活性呈剂量依赖性且具有统计学意义的降低。局部双侧向腹侧被盖区注射甘丙肽（2x1 nmol）而非伏隔核（2x2 nmol）也可产生对前脑多巴胺合成的影响。向蓝斑或背侧中缝核局部注射甘丙肽对前脑DOPA或5 - HTP积累无影响。结论是神经肽甘丙肽调节前脑多巴胺能神经传递。这种作用似乎是在中脑 - 新纹状体通路的胞体 - 树突水平介导的，或许可用于使归因于该神经元通路功能障碍（如精神分裂症）的紊乱正常化。
