Kappa opioid receptor agonists inhibit the pilocarpine-induced seizures and toxicity in the mouse.
Involvement of the kappa opioid receptor in regulation of the pilocarpine-induced seizures and neurodegeneration was studied in mice. Administration of pilocarpine (400 mg/kg i.p.) resulted in a sequence of behavioral alterations including motor limbic seizures. Pretreatment of mice with the selective kappa opioid receptor agonist U69,593 (2 and 20 mg/kg i.p.) or PD117,302 (0.1 and 1 mg/kg i.p.) increased the latency of motor seizures and decreased the seizure severity and mortality. Those effects were abolished in animals pretreated with the specific kappa opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 10 mg/kg i.p.). Examination of frontal forebrain sections by light microscopy revealed widespread damage, especially within the hippocampal formation, in pilocarpine-treated mice. Both U69,593 and PD117,503 protected the integrity of hippocampal neurons, especially in the CA1 region, that effect being reversed by Nor-BNI. The above data indicate that activation of the kappa opioid receptor exerts an inhibitory effect on the pilocarpine-induced limbic seizures and neurotoxicity.
Przewłocka
B
B
Neuropeptide Research Department, Polish Academy of Sciences, Cracow.
Machelska
H
H
Lasoń
W
W
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology; D007274:Injections, Intraperitoneal; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010862:Pilocarpine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D011758:Pyrroles / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013876:Thiophenes / Q000494:pharmacology
D000700:Analgesics; D044482:Benzeneacetamides; D011758:Pyrroles; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; D010862:Pilocarpine; C054718:PD 117302; C051844:norbinaltorphimine; D009271:Naltrexone; C045444:U 69593