Involvement of dopamine receptors in beneficial effects of tachykinins on scopolamine-induced impairment of alternation performance in mice.

The involvement of dopamine receptors in the beneficial effects of intracerebroventricular injection of substance P, neurokinin A and senktide on the scopolamine-induced impairment of spontaneous alternation performance was investigated in mice. Scopolamine (1 mg/kg) significantly impaired spontaneous alternation performance, while substance P (0.1 microg), neurokinin A (0.3 microg), senktide (0.003 microg) and S(-)-sulpiride (10 mg/kg), a dopamine D2 receptor antagonist, improved the scopolamine (1 mg/kg)-induced disturbance of spontaneous alternation performance. However, the dopamine D1 receptor antagonist SCH23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine maleate) did not influence the scopolamine-induced disturbance of spontaneous alternation performance. The dopamine D2 receptor agonist RU24213 (N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)-ethylamine hydrochloride) (1 mg/kg) but not the dopamine D1 receptor agonist SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride) (3 and 10 mg/kg) reversed the beneficial effects of substance P (0.1 microg) and neurokinin A (0.3 microg) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. In contrast, neither SKF38393 (3 and 10 mg/kg) nor RU24213 (0.3 and 1 mg/kg) significantly affected the beneficial effects of senktide (0.003 microg) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. Although RU24213 (1 mg/kg) and SCH23390 (0.03 mg/kg) markedly decreased total arm entries, SKF38393 (10 mg/kg), RU24213 (1 mg/kg), SCH23390 (0.03 mg/kg) or S(-)-sulpiride (10 mg/kg) had no significant effects on spontaneous alternation performance. These results suggest that stimulation of dopamine D2 but not D1 receptors reverses the ameliorative effects of substance P and neurokinin A, whereas neither dopamine D1 nor D2 receptors play an important role in the beneficial effects of senktide on the scopolamine-induced impairment of spontaneous alternation performance associated with spatial working memory.