Dopaminergic involvement in the improving effects of dynorphin A-(1-13) on scopolamine-induced impairment of alternation performance.
The present study was designed to clarify whether dopamine systems are involved in the effect of dynorphin A-(1-13), an endogenous kappa-opioid receptor agonist, on the scopolamine-induced impairment of spontaneous alternation performance related to working memory in mice. Sulpiride (10 and/or 30 mg/kg), a dopamine D2-selective antagonist, markedly improved the impairment of alternation performance and significantly reduced the increase in total arm entries (i.e. locomotor activity) induced by scopolamine (1 mg/kg). In contrast, SCH 23390 (0.01, 0.03 and 0.1 mg/kg), a dopamine D1-selective antagonist, did not influence the impairment of alternation performance, whereas it dose dependently reduced total arm entries in scopolamine-treated mice RU 24213 (1 mg/kg), a dopamine D2-selective agonist, almost completely reversed the improving effect of dynorphin A-(1-13) (3 micrograms) on the scopolamine-induced impairment of alternation performance and reduced total arm entries, although it was without effects on behavioral responses in normal mice. However, SKF 38393 (3 and 10 mg/kg), a dopamine D1-selective agonist, failed to change alternation performance or total arm entries in normal or scopolamine-treated mice. These findings suggest that the impairment of spontaneous alternation performance induced by scopolamine is improved by the blockade of dopamine D2 receptors. Furthermore, the improving effect of dynorphin A-(1-13) on the scopolamine-induced impairment of spontaneous alternation performance may be based upon the inhibition of dopaminergic activity through the mediation of kappa-opioid receptors.
Itoh
J
J
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Ukai
M
M
Kameyama
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013469:Sulpiride / Q000494:pharmacology
D000700:Analgesics; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D010446:Peptide Fragments; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017473:Receptors, Opioid, kappa; 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; C026843:dynorphin (1-13); D004399:Dynorphins; D013469:Sulpiride; D012601:Scopolamine; D004298:Dopamine