Increased striatal expression of glutamate decarboxylase 67 after priming of 6-hydroxydopamine-lesioned rats

Abstract

Previous single exposure (priming) to a dopamine receptor agonist greatly enhances the contralateral turning behaviour elicited by dopamine D 1 receptor agonists in unilaterally 6-hydroxydopamine lesioned rats. In the present study we have investigated the levels of glutamate decarboxylase 67 and glutamate decarboxylase 65 messenger RNA in the striatum of 6-hydroxydopamine-lesioned rats primed with l-3,4-dihydroxyphenylalanine ( l-DOPA) and challenged with the D 1 receptor agonist SKF 38393, three days thereafter. As previously reported, levels of glutamate decarboxylase 67 messenger RNA increased in the striatum denervated by the 6-hydroxydopamine lesion as compared with the intact one. Striatal glutamate decarboxylase 67 messenger RNA levels, measured three days after priming with l-DOPA (50 mg/kg), further increased in the lesioned striatum while were not modified in the intact one. Administration of SKF 38393 (3 mg/kg) elicited a more intense contralateral turning behaviour in primed than in drug-naive 6-hydroxydopamine-lesioned rats but did not induce any change in striatal glutamate decarboxylase 67 messenger RNA. In contrast, striatal levels of glutamate decarboxylase 65 messenger RNA were not modified by either 6-hydroxydopamine lesions or priming with l-DOPA. The results show that priming with l-DOPA induces long-lasting changes in GABAergic neurons of the 6-hydroxydopamine-lesioned striatum. These changes might play a role in the increased behavioural response of striatal D 1 receptors induced by priming.