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.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
M
M
Ukai
N
N
Shinkai
T
T
Kameyama
D000647:Amnesia / Q000139:chemically induced* / Q000523:psychology; D000818:Animals; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D015288:Neurokinin A / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D018041:Receptors, Neurokinin-2 / Q000819:agonists* / Q000502:physiology; D018042:Receptors, Neurokinin-3 / Q000819:agonists* / Q000502:physiology; D012601:Scopolamine; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology
D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; D015288:Neurokinin A; D012601:Scopolamine