Effects of the kappa-opioid dynorphin A(1-13) on learning and memory in mice.
The effects of intracerebroventricular administration of dynorphin A(1-13) on scopolamine- and pirenzepine-induced amnesia were investigated in mice by observing the step-down-type passive avoidance response and spontaneous alternation performance. The pre- or post-training, or preretention administration of dynorphin A(1-13) (0.3-10 micrograms) alone failed to affect the passive avoidance response, while scopolamine (1 mg/kg) significantly inhibited it. Dynorphin A(1-13) (1 microgram) given 15 min before training and retention tests, but not immediately after training, significantly improved the scopolamine (1 mg/kg)-induced impairment of passive avoidance response, indicating the anti-amnesic effects of dynorphin A(1-13). A lower dose (1 mg/kg) of the kappa-opioid receptor antagonist (-)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomorpha n reversed the anti-amnesic effects of dynorphin A(1-13) (1 microgram). In contrast, although dynorphin A(1-13) (1, 3 and 10 micrograms) did not influence spontaneous alternation performance, scopolamine (1 mg/kg) and the muscarinic M1 receptor antagonist pirenzepine (3 micrograms) markedly decreased spontaneous alternation performance. Dynorphin A(1-13) (3, 5.6 and/or 10 micrograms) significantly improved the scopolamine (1 mg/kg)- and pirenzepine (3 micrograms)-induced impairment of spontaneous alternation performance. The improving effects of dynorphin A(1-13) (3 micrograms) were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms), a kappa-selective opioid receptor antagonist. These results suggest that the stimulation of kappa-opioid receptors improves memory dysfunctions resulting from the blockade of muscarinic M1 receptors.
Ukai
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Itoh
J
J
Kobayashi
T
T
Shinkai
N
N
Kameyama
T
T
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004399:Dynorphins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D018727:Muscarinic Antagonists; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010890:Pirenzepine; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D012601:Scopolamine
D000701:Analgesics, Opioid; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D010890:Pirenzepine; D009271:Naltrexone; C026843:dynorphin (1-13); D004399:Dynorphins; D012601:Scopolamine