Quantification of neuromodulin (GAP-43, B-50) and synapsin I in rat striata

We reported previously that phosphorylated neuromodulin and phosphorylated synapsin I content increased in the striata of amphetamine-sensitized rats; however, the neuronal pathways responsible for the increase were unclear. In the present study, changes in neuromodulin and synapsin I content resulting from the manipulation of lesions were quantified to elucidate the responsible pathways. Nerve terminals originating in the corticostriatal pathway, those from the nigrostriatal pathway and those from interneurons in the striatum, were impaired by unilateral cortical ablation, 6-hydroxydopamine (6-OHDA) treatment and kainic acid injection into the striatum, respectively. Neuromodulin and synapsin I content in the ipsilateral striatum after unilateral ablation of the frontal cortex decreased by 51 and 31%, respectively. The impairment of dopaminergic terminals by 6-OHDA reduced the neuromodulin content by 22%; however, no significant alteration was observed in the synapsin I content as the result of 6-OHDA treatment. The injection of kainic acid did not cause the content of either protein to decrease. These results suggest that corticostriatal nerve terminals possess a large part of the total neuromodulin and almost all the synapsin I in the striatum. Therefore, the increase in phosphorylated neuromodulin induced by repeated treatment with amphetamine may occur in corticostriatal glutamatergic terminas and/or nigrostriatal dopaminergic terminals. On the other hand, the increase in phosphorylated synapsin I may preferentially occur in the corticostriatal glutamatergic terminals.