The effect of pentylenetetrazol kindling on synaptic mechanisms of interacting glutamatergic and opioid system in the hippocampus of rats.
Endogenous opioids modulate processes of central excitability such as long-term potentiation and electrical kindling. Little is known about the neurochemical alterations in the interaction of the glutamatergic and opioid system in the development of pentylenetetrazol (PTZ) kindling in rats. Therefore, in the present study we investigated glutamate, DAMGO and naltrindole receptor binding, receptor protein expression by Western blot and ex vivo glutamate transmitter release in PTZ kindled rats. The specific 3H-DAMGO and -naltrindole binding to hippocampal membranes displayed no significant changes in kindled rats compared to controls. In contrast, the 3H-l-glutamate binding was significantly enhanced after completion of PTZ kindling. The expression of receptor protein for glutamate as well as the naloxone- and naltrindole-induced 3H-d-aspartate release from hippocampal slices did not alter in any case as a consequence of PTZ kindling. The PTZ induced enhancement of the glutamate binding sites in the hippocampus was downregulated to control level by natrindole treatment of rats prior to each PTZ application. Furthermore, naltrindole pretreatment of rats significantly inhibited the development of seizure susceptibility. In contrast, naloxone was not able to alter the seizure activity induced by PTZ as well as the transmitter receptor binding. The results are discussed in the light of a modulating role of delta-opioid receptors in PTZ kindling.
Schroeder
H
H
Institute of Pharmacology and Toxicology, Medical Faculty, Otto-von-Guericke-University, D-39120-, Magdeburg, Leipziger Str. 44, Germany.
Becker
A
A
Grecksch
G
G
Schroeder
U
U
Hoellt
V
V
D000818:Animals; D003292:Convulsants / Q000633:toxicity; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007696:Kindling, Neurologic; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D012640:Seizures / Q000188:drug therapy; D013569:Synapses / Q000187:drug effects*
D003292:Convulsants; D004745:Enkephalins; D009292:Narcotic Antagonists; D017470:Receptors, Glutamate; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D009271:Naltrexone; C055382:naltrindole; D010433:Pentylenetetrazole