Dopaminergic involvement in the improving effects of dynorphin A-(1-13) on scopolamine-induced impairment of alternation performance.

The present study was designed to clarify whether dopamine systems are involved in the effect of dynorphin A-(1-13), an endogenous kappa-opioid receptor agonist, on the scopolamine-induced impairment of spontaneous alternation performance related to working memory in mice. Sulpiride (10 and/or 30 mg/kg), a dopamine D2-selective antagonist, markedly improved the impairment of alternation performance and significantly reduced the increase in total arm entries (i.e. locomotor activity) induced by scopolamine (1 mg/kg). In contrast, SCH 23390 (0.01, 0.03 and 0.1 mg/kg), a dopamine D1-selective antagonist, did not influence the impairment of alternation performance, whereas it dose dependently reduced total arm entries in scopolamine-treated mice RU 24213 (1 mg/kg), a dopamine D2-selective agonist, almost completely reversed the improving effect of dynorphin A-(1-13) (3 micrograms) on the scopolamine-induced impairment of alternation performance and reduced total arm entries, although it was without effects on behavioral responses in normal mice. However, SKF 38393 (3 and 10 mg/kg), a dopamine D1-selective agonist, failed to change alternation performance or total arm entries in normal or scopolamine-treated mice. These findings suggest that the impairment of spontaneous alternation performance induced by scopolamine is improved by the blockade of dopamine D2 receptors. Furthermore, the improving effect of dynorphin A-(1-13) on the scopolamine-induced impairment of spontaneous alternation performance may be based upon the inhibition of dopaminergic activity through the mediation of kappa-opioid receptors.