Differential effects of mu-opioid receptor agonists in a hippocampal hypoxia/hypoglycemia model.
BACKGROUND
In rat hippocampal slices, a short hypoxia/hypoglycemia causes immediate loss of evoked potentials (population spike amplitude) in the CA1 region and the extent of electrophysiological restoration during reperfusion can serve as a parameter for cell function. Previous experiments using this model revealed that exposure to morphine aggravates the neurotoxic effects of a subsequent hypoxia/hypoglycemia in a concentration-dependent manner. Therefore, the aim of the present study was to evaluate the effects of additional mu-opioid receptor (MOPr) agonists on the electrophysiological restoration after hypoxia/hypoglycemia.


METHODS
Rat hippocampal slices were exposed to either morphine (10 microM), pethidine (10 microM), fentanyl (100 nM/1 microM) or to the synthetic peptide [d-Ala2, N-Me-Phe4, Glycinol5]-enkephalin (DAMGO, 10 microM) for 60 min; thereafter, slices underwent a brief hypoxic/hypoglycemic episode followed by reperfusion (drug-free) for 2.5 h. Electrophysiological recording consisted of determination of population spike amplitude in CA1 in response to constant stimulation of Schäffer's collaterals.


RESULTS
Exposure to morphine prior to hypoxia/hypoglycemia resulted in a significantly impaired electrophysiological recovery during reperfusion when compared to controls. Following exposure to pethidine, the electrophysiological recovery was slightly reduced, whereas fentanyl or DAMGO did not affect restoration of population spike amplitude during reperfusion.


CONCLUSIONS
The results of the present study demonstrate that different MOPr agonists differentially influence the electrophysiological recovery of hippocampal slices following a brief hypoxia/hypoglycemia. It is speculated that known receptor-internalizing opioids such as fentanyl or DAMGO may have less neurotoxic effect in hypoxia/hypoglycemia than the non-internalizing drug morphine.
Ammon-Treiber
Susanne
S
Institute of Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. susanne.ammon-treiber@uniklinikum-saarland.de <susanne.ammon-treiber@uniklinikum-saarland.de>
Stolze
Daniela
D
Höllt
Volker
V
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005283:Fentanyl / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007003:Hypoglycemia / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists*; D015427:Reperfusion Injury / Q000503:physiopathology
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D008614:Meperidine; D005283:Fentanyl