Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice.

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.