The effects of dopamine D-1 and D-2 receptor subtype agonists on nigrostriatal opioid dynorphin and enkephalin immunostaining in 6-hydroxydopamine lesioned rats

Abstract

Using selective neurotoxin lesioning and immunocytochemical techniques, the effects of dopamine receptor subtypes stimulation by selective subtype agonists in the modulation of striatal opioid dynorphin and enkephalin were characterized in the rat basal ganglia. Tissue staining with specific antibodies against either dynorphin A (1-17) or [Met5]-enkephalin was examined in the striatum and substantia nigra following unilateral nigrostriatal dopaminergic lesioning by the neurotoxin 6-hydroxydopamine (6-OHDA). Two weeks later three groups of five 6-OHDA lesioned rats were repeatedly treated with either the dopamine D-1 receptor agonist SKF-38393 (5 mg.kg, i.p.), D-2 receptor agonist LY-171555 (1 mg/kg, i.p.) or saline for 7 days and similar immunostaining procedures were employed. The results indicated that 6-OHDA lesioning alone led to reduction in dynorphin A (1-17) immunostaining in substantia nigra and striatum when compared to the sham-lesioned contralateral side. However, SKF-38393 treatment reversed that pattern and caused more intense dynorphin A (1-17) immunostaining than the lesion side, while LY-171555 had no effect. In contrast, enkephalin immunostaining was increased by 6-OHDA lesioning, and the effect was abolished by SKF-38393 but not LY-171555. These results are in agreement with previously reported radioimmunoassay findings and are compatible with the proposal that dopamine D-1 receptors mediate the excitatory effect on the dynorphinergic system while inhibiting the enkephalinergic system.