Dynorphin A-(1-13) potently improves scopolamine-induced impairment of passive avoidance response in mice.
The effects of intracerebroventricular administration of dynorphin A-(1-13) on scopolamine-induced amnesia were investigated in mice by using a step-down type passive avoidance task. The pre- or post-training, or pre-retention administration of dynorphin A-(1-13)(0.3-10 micrograms) alone failed to affect step-down latency of the passive avoidance response, while scopolamine (1 mg/kg) significantly shortened step-down latency. 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 shortening of step-down latency of the passive avoidance response, indicating antiamnesic effects of dynorphin A-(1-13) (1 microgram). 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-benzomorphan, reversed the anti-amnesic effects of dynorphin A-(1-13) (1 microgram). These results suggest that the antiamnesic effects of dynorphin A-(1-13) depend on the timing of drug treatments.
Ukai
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Kobayashi
T
T
Shinkai
N
N
Shan-Wu
X
X
Kameyama
T
T
D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D012601:Scopolamine / Q000008:administration & dosage / Q000633:toxicity*; D013237:Stereoisomerism
D000701:Analgesics, Opioid; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; C026843:dynorphin (1-13); D004399:Dynorphins; D012601:Scopolamine