Dynorphin A-(1-13) potently prevents memory dysfunctions induced by transient cerebral ischemia in mice.
The effect of dynorphin A-(1-13), an endogenous kappa-opioid receptor agonist, on memory dysfunctions induced by transient cerebral ischemia in mice was investigated by using three different tasks, namely, spontaneous alternation, elevated plus-maze performance, and passive avoidance behavior. Transient ischemia produced a marked memory dysfunction in mice, as assessed in the three tasks, which were carried out consecutively 1 to 3 days after the ischemic insult. The i.c.v. injection of dynorphin A-(1-13) before the ischemic insult potently prevented the impairment of spontaneous alternations, the prolongation of transfer latency in the elevated plus-maze and the shortening of step-through latency in the passive avoidance task induced by transient ischemia. Dynorphin A-(1-13) (10 micrograms), however, did not affect the body temperature of the sham-operated or the ischemic mice. The protective effect of dynorphin A-(1-13) (10 micrograms) on ischemia-induced memory dysfunctions observed in the three tasks was almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-selective opioid receptor antagonist. These results suggest that dynorphin A-(1-13) prevents memory dysfunctions in ischemic mice through the activation 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
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004399:Dynorphins / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000523:psychology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000494:pharmacology*
D010446:Peptide Fragments; C026843:dynorphin (1-13); D004399:Dynorphins