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.
Ukai
M
M
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan. ukai@meijo-u.ac.jp
Shinkai
N
N
Kameyama
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D015288:Neurokinin A / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012601:Scopolamine; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010446:Peptide Fragments; D010627:Phenethylamines; D011950:Receptors, Cholinergic; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015320:Tachykinins; C054724:senktide; D013373:Substance P; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D013469:Sulpiride; D015288:Neurokinin A; D012601:Scopolamine