Dynorphin modulates dopamine D1-receptor mediated turning behavior in 6-hydroxydopamine-lesioned rats

We investigated if the potentiated turning response to a challenge with the partial dopamine D1 receptor agonist SKF-38393, as seen after priming with L-dihydroxyphenytalanine (DOPA) of unilaterally 6-hydroxydopamine-lesioned rats, can be modulated by infusion of dynorphin A (1-17) in the striatum. Seventeen days after the 6-hydroxydopamine lesion, rats received intrastria tal dynorphin (0.08 or 3.85 mu g) followed by L-DOPA (50 mg/kg i.p.) and we re challenged 3 days later with SKF-38393 (3.0 mg/kg s.c.). Compared to con trols, the lower dose of dynorphin caused an earlier onset of turning, whil e the higher dose decreased the response to SKF-38393. These findings sugge st a dose-dependent modulatory role for striatal dynorphin in L-DOPA-primin g of a D1-mediated behavioral response. (C) 2000 Elsevier Science Ireland L td. All rights reserved.