neurokinin-a and Amnesia

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.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amnesia; Animals; Benzazepines; Dopamine Agonists; Dopamine Antagonists; Male; Memory; Mice; Neurokinin A; Peptide Fragments; Phenethylamines; Receptors, Cholinergic; Receptors, Dopamine D1; Receptors, Dopamine D2; Scopolamine; Substance P; Sulpiride; Tachykinins

The effects of intracerebroventricular injections of the neurokinin-2 (NK-2) receptor agonist neurokinin A and the neurokinin-3 (NK-3) receptor agonist senktide on scopolamine (sc)-induced amnesia were investigated based on spontaneous alternation performance in mice. Spontaneous alternation performance is based on spatial working memory which produces a natural tendency to explore a less recently visited arm in a Y-maze. Neurokinin A (0.1-3 micrograms) or senktide (0.0003-0.03 microgram) alone did not influence either spontaneous alternation performance or total arm entries. However, neurokinin A (0.3 and 1 microgram) and senktide (0.003 and 0.03 microgram) inhibited the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting the scopolamine (1 mg/kg)-induced increase in total arm entries. Although the effects of neurokinin A (0.3 microgram) on the scopolamine-induced impairment of spontaneous alternation performance were almost completely antagonized by pretreatment with the NK-2 receptor antagonist cyclo (Gln-Trp-Phe-Gly-Leu-Met) (1 microgram), the inhibitory effects of senktide (0.003 microgram) were not influenced by pretreatment with the NK-3 receptor antagonist [Trp7, beta-Ala8]neurokinin A-(4-10). These findings suggest that neurokinin A inhibits the scopolamine-induced impairment of spontaneous alternation performance associated with working memory through the mediation of tachykinin NK-2 receptors, while senktide has some pharmacological action other than its effects on NK-3 receptors.

Topics: Amnesia; Animals; Male; Maze Learning; Mice; Neurokinin A; Peptide Fragments; Psychomotor Performance; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Scopolamine; Substance P