Summary
The effects of a pharmacological blockade of the mu opiate receptors on the manifestation of tonic-clonic seizures were investigated in freely moving animals. 4-aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult rats with 1 mg/kg naltrexone HCl, 3, 5, 7, 9, 14 mg/kg 4-aminopyridine was injected intraperitoneally, and the latencies of the symptoms generated by 4-aminopyridine were measured. Naltrexone HCl decreased these latencies and enhanced the seizures significantly. The experiments provided further evidence for the existence of a tonic anticonvulsant opioid system in the brain.
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Andén N-E, Leander S (1979) Effects of 4-aminopyridine on the turnover of monoamines in the central nervous system of the rat. J Neural Transm 44: 1–12
Baranowska B, Rozbicka G, Jeske W, Abdel-Fattah MH (1984) The role of endogenous opiates in the mechanism of inhibited luteinizing hormone (LH) secretion in women with anorexia nervosa: the effect of naloxone on LH, follicle-stimulating hormone, prolactin and β-endorphin secretion. J Clin Endocrinol Metab 59: 412–416
Casamenti F, Corradetti R, Löffelholz K, Mantovani P, Pepeu G (1982) Effects of 4-aminopyridine on acetylcholine output from the cerebral cortex of the ratin vivo. Br J Pharmacol 76: 439–445
Coleman JC, Shenoy AK, Chweh AY, Swinyard EA (1985) An analysis of thein vivo interactions between chemical convulsants and anticonvulsants. Life Sci 37: 749–755
Corcoran ME, Wada JA (1979) Naloxone and the kindling of seizures. Life Sci 24: 791–796
Cowan A, Geller EB, Adler MW (1979) Classification of opioids on the basis of change in seizure threshold in rats. Science 206: 465–467
De Graan PNE, Schrama LH, Brussaard AB, Jork R, Gispen WH (1987) 4-aminopyridine affects synaptosomal protein phosphorylation in rat hippocampal slices. Brain Res 404: 345–349
Dingledine R, Iversen LL, Breuker E (1978) Naloxone as a GAB A antagonist: evidence from iontophoretic, receptor binding and convulsant studies. Eur J Pharmacol 47: 19–27
Ennis C, Stephens RJ (1984) A comparison of the effects of meptazinol and morphine on the release of acetylcholine from slices of mouse cerebral cortex. Neuropharmacology 23: 1431–1433
Foldes FF, Ludvig N, Nagashima H, Vizi ES (1988) The influence of aminopyridines on Ca2+-dependent evoked release of acetylcholine from rat cortex slices. Neurochem Res 13: 761–764
Frenk H (1983) Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems. Brain Res Rev 6: 197–210
Gruol DL, Barker JL, Smith TG (1980) Naloxone antagonism of GABA-evoked membrane polarizations in cultured mouse spinal cord neurons. Brain Res 198: 323–332
Hagan RM, Hughes IE (1984) Opioid receptor sub-types involved in the control of transmitter release in cortex of the brain of the rat. Neuropharmacology 23: 491–495
Haxthausen EF von (1955) Über Amino-Pyridin und seine Derivate. Arch Exp Pathol Pharmakol 226: 163–171
Höllt V, Przewlocki R, Herz A (1978) β-Endorphin-like immunoreactivity in plasma, pituitaries and hypothalamus of rats following treatment with opiates. Life Sci 23: 1057–1066
Kelsey JE, Belluzzi JD (1982) Endorphin mediation of postictal effects of kindled seizures in rats. Brain Res 253: 337–340
Kosten TR, Kreek M-J, Ragunath J, Kleber HD (1986) A preliminary study of beta endorphin during chronic naltrexone maintenance treatment in ex-opiate addicts. Life Sci 39: 55–59
Kosterlitz HW (1985) The Wellcome Foundation Lecture, 1982. The opioid peptides and their receptors. Proc R Soc Lond B225: 27–40
Lai WS, Ramkumar V, El-Fakahany EE (1985) Possible allosteric interaction of 4-aminopyridine with rat brain muscarinic acetylcholine receptors. J Neurochem 44: 1936–1942
Lemeignan M, Millart H, Lamiable D, Molgo J, Lechat P (1984) Evaluation of 4-aminopyridine penetrability into cerebrospinal fluid in anesthetized rats. Brain Res 304: 166–169
Lewis ME, Pert A, Pert CB, Herkenham M (1983) Opiate receptor localization in rat cerebral cortex. J Comp Neurol 216: 339–358
Llinás R, Walton K, Sugimori M, Simon S (1982) 3- and 4-aminopyridine in synaptic transmission at the squid giant synapse. In: Lechat P, Thesleff S, Bowman WC (eds) Aminopyridines and similarly acting drugs: effects on nerves, muscles and synapses. Pergamon Press, Oxford, pp 69–79
Magnan J, Paterson SJ, Tavani A, Kosterlitz HW (1982) The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn-Schmiedebergs Arch Pharmacol 319: 197–205
Matsumoto M, Riker WK (1983) Synaptic transmission in low extracellular calcium is preserved by 3,4-diaminopyridine. J Pharmacol Exp Therap 227: 16–21
McLean S, Rothman RB, Herkenham M (1986) Autoradiographic localization of μ- and δ-opiate receptors in the forebrain of the rat. Brain Res 378: 49–60
Mihály A, Bencsik K, Solymosi T (1987) Pharmacology of convulsions mediated by potassium channels: the role of benzodiazepine and opiate receptors. Neuroscience 22 [Suppl]: 1982P
Morris BJ, Herz A (1987) Distinct distribution of opioid receptor types in rat lumbar spinal cord. Naunyn-Schmiedebergs Arch Pharmacol 336: 240–243
Nicoll RA, Siggins GR, Ling N, Bloom FE, Guillemin R (1977) Neuronal actions of endorphins and enkephalins among brain regions: a comparative microiontophoretic study. Proc Natl Acad Sci USA 74: 2584–2588
Pasantes-Morales H, Arzate ME, Quesada O, Huxtable RJ (1987) Higher susceptibility of taurine-deficient rats to seizures induced by 4-aminopyridine. Neuropharmacology 26: 1721–1725
Perkins MN, Stone TW (1980) 4-Aminopyridine blockade of neuronal depressant responses to adenosine triphosphate. Br J Pharmacol 70: 425–428
Puglisi-Allegra S, Cabib S, Oliverio A (1985) Pharmacological evidence for a protective role of the endogenous opioid system on electroshock-induced seizures in the mouse. Neurosci Lett 62: 241–247
Racké K, Altes U, Baur A-M, Jost D, Schäfer J (1987) Tetraethylammonium ions and 4-aminopyridine prevent opioid inhibition of neurohypophysial oxytocin release. Brain Res 436: 371–373
Rogawski MA (1985) The A-current: how ubiquitous a feature of exitable cells is it? Trends Neurosci 8: 214–219
Rogawski MA, Barker JL (1983) Effects of 4-aminopyridine on calcium action potentials and calcium current under voltage clamp in spinal neurons. Brain Res 280: 180–185
Sagratella S, Massotti M (1982) Convulsant and anticonvulsant effects of opioids: relationship to GABA-mediated transmission. Neuropharmacology 21: 991–1000
Spillantini MG, Massotti M (1986) Inhibition of penicillin-induced EEG discharges by low doses of morphine or naloxone in the rabbit. Evidence for a possible non-opioid receptor-mediated mechanism at the sensorimotor cortex. Pharmacol Biochem Behav 24: 1241–1246
Szente M, Baranyi A (1987) Mechanism of aminopyridine-induced ictal seizure activity in the cat neocortex. Brain Res 413: 368–373
Tallarida RJ, Jacob LS (1979) The dose-response relation in pharmacology. Springer, Berlin Heidelberg New York
Tempel A, Gardner EL, Zukin RS (1984) Visualization of opiate receptor upregulation by light microscopy autoradiography. Proc Natl Acad Sci USA 81: 3893–3897
Thesleff S (1980) Aminopyridines and synaptic transmission. Neuroscience 5: 1413–1419
Urca G, Yitzhaky J, Frenk H (1981) Different opioid systems may participate in post-electroconvulsive shock (ECS) analgesia and catalepsy. Brain Res 219: 385–396
Wardlaw AC (1985) Practical statistics for experimental biologists. Wiley, New York
Williams JT, Egan TM, North RA (1982) Enkephalin opens potassium channels. Nature 299: 74–77
Wüster M, Schulz R, Herz A (1980) Inquiry into endorphinergic feedback mechanisms during the development of opiate tolerance/dependence. Brain Res 189: 403–411
Zukin RS, Sugarman JR, Fitz-Syage ML, Gardner EL, Zukin SR, Gintzler AR (1982) Naltrexone-induce opiate receptor supersensitivity. Brain Res 245: 285–292
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Mihály, A., Bencsik, K. & Solymosi, T. Naltrexone potentiates 4-aminopyridine seizures in the rat. J. Neural Transmission 79, 59–67 (1990). https://doi.org/10.1007/BF01251001
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DOI: https://doi.org/10.1007/BF01251001