Delta opioid receptors stimulation with [D-Ala2, D-Leu5] enkephalin does not provide neuroprotection in the hippocampus in rats subjected to forebrain ischemia.
It has been reported that delta opioid agonists can have neuroprotective efficacy in the central nervous system. This study was conducted to test the hypothesis that a delta opioid receptor (DOR) agonist, [D-Ala2, D-Leu5] enkephalin (DADLE), can improve neuron survival against experimental forebrain ischemia in rats. Using male rats (n=125), intraperitoneal injection of DADLE (0, 0.25, 1, 4, 16 mg kg-1) was performed 30 min before ischemia. Ten minutes interval forebrain ischemia was provided by the bilateral carotid occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. All animals were neurologically and histologically evaluated after a recovery period of 1 week. As histological evaluation, percentages of ischemic neurons in the CA1, CA3, dentate gyrus (DG) were measured. During the recovery period, 27 rats died because of apparent upper airway obstruction, seizure, or unidentified causes. There were no differences in the motor activity score among the groups. Ten minutes forebrain ischemia induced approximately 75, 20, and 10% neuronal death in the CA1, CA3, and DG, respectively. Any doses of DADLE did not attenuate neuronal injury in the hippocampus after ischemia. Pre-ischemic treatment of DORs agonism with DADLE did not provide any neuroprotection to the hippocampus in rats subjected to forebrain ischemia.
Iwata
Masato
M
Department of Anesthesiology, Nara Medical University, 840 Shijo-cho Kashihara, Nara 634-8522, Japan.
Inoue
Satoki
S
Kawaguchi
Masahiko
M
Kurita
Naoko
N
Horiuchi
Toshinori
T
Nakamura
Mitsutoshi
M
Konishi
Noboru
N
Furuya
Hitoshi
H
D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D017211:Treatment Failure
D000701:Analgesics, Opioid; D018696:Neuroprotective Agents; D017465:Receptors, Opioid, delta; D016308:Enkephalin, Leucine-2-Alanine