THE STRIATONIGRAL DYNORPHIN PATHWAY OF THE RAT STUDIED WITH IN-VIVO MICRODIALYSIS .2. EFFECTS OF DOPAMINE D-1 AND D-2 RECEPTOR AGONISTS

In vivo microdialysis was used to study the effect of intracerebral ad ministration of dopamine agonists on dynorphin B release in the striat um and substantia nigra of rats. The release of dopamine and GABA was also investigated. Administration of the dopamine D-1 agonist SKF 3839 3 (10-100 mu M) into the striatum increased extracellular dynorphin B and GABA levels in the ipsilateral substantia nigra, in a concentratio n-dependent manner. After a short-lasting increase, nigral dopamine le vels were significantly decreased after the highest concentration of s triatal SKF 38393. An increase in striatal dynorphin B, GABA and dopam ine levels was also observed. When SKF 38393 (10 mu M) was administere d into the substantia nigra, nigral dynorphin B and GABA, but not dopa mine levels increased. No significant effects were observed on striata l levels. Administration of the dopamine D-2 agonist, quinpirole (100 mu M), into the striatum decreased dopamine levels in both striatum an d substantia nigra, while no effect was observed on striatal or nigral dynorphin B and GABA levels. Quinpirole (10-100 mu M) given into the substantia nigra, decreased striatal dopamine levels in a concentratio n manner. In the nigra, a short-lasting increase in dopamine levels wa s observed following the highest concentration of nigral quinpirole (1 00 mu M). The effect was followed by a decrease in dopamine levels. No significant effects were observed on striatal or nigral dynorphin B a nd GABA levels. The results show that stimulation of D-1 receptors in striatum and substantia nigra leads to activation of the striatonigral dynorphin pathway. A parallel effect could also be seen on nigral GAB A release. In contrast, D-2 receptor stimulation primarily leads to in hibition of the nigrostriatal dopamine pathway, probably via autorecep tors located on striatal dopamine terminals and on nigral dopamine den drites.