Abstract
Selective depletion of forebrain noradrenaline has been shown to potentiate various types of experimentally induced seizures. This study was aimed at exploring the role of different types of adrenergic receptors in pentylenetetrazol (PTZ)-induced seizures in rats and the anticonvulsive effect of di-n-propylacetate (DPA). Piperoxane (10 and 20 mg/kg, IP) significantly potentiated PTZ-induced tonic seizures and mortality. Similar effects were observed after 6-hydroxydopamine (6-OHDA)-induced depletion of forebrain noradrenaline, whereas no effects were found in animals with depletion of spinal noradrenaline. Neither phenoxybenzamine (20 mg/kg, IP) nor prazosin (1 and 10 mg/kg, IP) nor propranolol (2 and 5 mg/kg, IP) modified tonic seizures and mortality caused by PTZ. Combined treatment with propranolol (5 mg/kg, IP) and prazosin (10 mg/kg, IP) had no effect either. Various agents used to increase central serotonin transmission (d-fenfluramine, 5 mg/kg, IP; quipazine, 10 mg/kg, IP; m-chlorophenylpiperazine, 3 mg/kg, IP) did not alter the effect of piperoxane on PTZ-induced seizures. None of the conditions used to diminish central adrenergic, function significantly affected the inhibitory effect of DPA on tonic seizures and mortality caused by PTZ. Combined treatment with subthreshold doses of clonidine (0.1 mg/kg, IP) and DPA (75 mg/kg, IP) significantly reduced tonic seizures and mortality caused by PTZ. The data suggest that alpha2 type adrenoceptors are involved in the control of PTZ-induced seizures in rats. The peculiarity of the role of these receptors in the effect of PTZ is discussed.
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References
Andén N-E, Corrodi H, Fuxe K, Hokfelt B, Hokfelt T, Rydin C, Svensson T (1970) Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci 9:513–523
Andén N-E, Grabowska M, Strömbom U (1976) Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Arch Pharmacol 292:43–52
Andén N-E, Gomes C, Persson B, Trolin G (1978) R 28935 and prazosin: Effects on central and peripheral alpha-adrenoreceptor activity and on blood pressure. Naunyn-Schmiedeberg's Arch Pharmacol 302:299–306
Baldino F Jr, Geller HM (1981) Sodium valproate enhancement of γ-aminobutyric acid (GABA) inhibition: Electrophysiological evidence for anticonvulsant activity. J Pharmacol Exp Ther 217:445–450
Baraban JM, Aghajanian GK (1980) Supression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists. Neuropharmacology 19:355–363
Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC (1964) A new adrenergic beta-receptor antagonist Lancet I:1080–1081
Bolme P, Corrodi H, Fuxe K, Hokfelt T, Lidbrink P, Goldstein M (1974) Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Eur J Pharmacol 28:89–94
Braestrup C, Nielsen M (1976) Regulation in the central norepinephrine neurotransmission induced in vivo by alpha adrenoceptor active drugs. J Pharmacol Exp Ther 98:596–608
Browing RA, Hoffmann WE, Simonton RL (1978) Changes in seizure susceptibility after intracerebral treatment with 5,7-dihydroxyryptamine: Role of serotonergic neurons. Ann NY Acad Sci 305:437–456
Caccia S, Guiso G, Ballabio M, De Ponte P (1979) Simultaneous determination of the propranolol enantiomers in biological samples by gas-liquid chromatography. J Chromatogr 172:457–462
Callaghan DA, Schwark WS (1979) Involvement of catecholamines in kindled amygdaloid convulsions in the rat. Neuropharmacology 18:541–545
Corcoran ME, Mason ST (1980) Role of forebrain catecholamines in amygdaloid kindling. Brain Res 190:473–484
Crunelli V, Cervo L, Samanin R (1981) Evidence for a preferential role of central noradrenergic neurons in electrically induced convulsions and activity of various anticonvulsants in the rat. In: Morselli PL, Lloyd KG, Löscher W, Meldrum B, Reynolds EH (eds) Neurotransmitters, seizures, and epilepsy. Raven Press, New York, pp 195–202
De La Torre JC, Kanagawa HM, Mullan S (1970) Seizure susceptibility after manipulation of brain serotonin. Arch Int Pharmacodyn Ther 188:298–304
Fuxe K, Farnebo L-O, Hamberger B, Ögren S-O (1975) On the in vivo and in vitro actions of fenfluramine and its derivatives on central monoamine neurons, especially 5-hydroxytryptamine neurons and their relation to the anorectic activity of fenfluramine. Postgrad Med J 51 suppl 1:35–45
Gallager DW, Aghajanian GK (1976) Effect of antipsychotic drugs on the firing of dorsal raphe cells. I. Role of adrenergic system. Eur J Pharmacol 39:341–355
Garattini S, Buczko W, Jori A, Samanin R (1975) The mechanism of action of fenfluramine. Postgrad Med J 51 suppl 1:27–35
Greengrass P, Bremer R (1979) Binding characteristics of 3H-prazosin to rat brain α-adrenergic receptors. Eur J Pharmacol 55:323–326
Hammond EJ, Wilder BJ, Bruni J (1981) Central actions on valproic acid in man and in experimental models of epilepsy. Life Sci 29:2561–2574
Iadarola MJ, Gale K (1979) Dissociation between drug-induced increases in nerve terminal and non-nerve terminal pools of GABA in vivo. Eur J Pharmacol 59:125–129
Invernizzi R, Cotecchia S, De Blasi A, Mennini T, Pataccini R, Samanin R (1981) Effects of m-chlorophenylpiperazine on receptor binding and brain metabolism of monoamines in rats. Neurochem Int 3:239–244
Jobe PC, Picchioni AL, Chin L (1973) Role of brain norepinephrine in audiogenic seizure, in the rat. J Pharmacol Exp Ther 184:1–10
Keller R, Oke A, Mefford I, Adams RN (1976) Liquid chromatographic analysis of catecholamines routine assay for regional brain mapping. Life Sci 19:995–1004
Kerwin RW, Olpe H-R (1980) The effect of sodium valproate on single unit activity in the rat brain. Br J Pharmacol 70:76P
Kilian M, Frey H-H (1973) Central monoamines and convulsive thresholds in mice and rats. Neuropharmacology 12:681–692
König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Williams and Wilkins. Baltimore
Kupferberg HJ (1980) Antiepileptic drugs. Sodium valproate. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: Mechanisms of action. Raven Press, New York, pp 643–654
Langer SZ (1977) Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol 60:481–497
Lazarova M, Samanin R (1983) Serotonin mediation of the protective effect of clonidine against pentylenetetrazol-induced seizures in rats. Life Sci 32:2343–2348
Lazarova M, Bendotti C, Samanin R (1983) Studies on the role of serotonin in different regions of the rat central nervous system on pentylenetetrazol-induced seizures and the effect of di-N-propylacetate. Naunyn-Schmiedeberg's Arch Pharmacol 322:147–152
Le Fur G, Mitrani N, Uzan A (1977) Effects, of 4-(3-indolyl-alkyl) piperidine derivatives on brain 5-hydroxytryptamine turnover and on cardiac and brain noradrenaline or 5-hydroxytryptamine depletion induced by 6-hydroxydopamine H 75/12 and 4-chloroamphetamine. Biochem Pharmacol 26:505–509
Löscher W (1981) Effect of inhibitors of GABA aminotransferase on the metabolism of GABA in brain tissue and synaptosoma, fractions. J Neurochem 36:1521–1527
Mason ST, Corcoran ME (1979a) Catecholamines and convulsions. Brain Res 170:497–507
Mason ST, Corcoran ME (1979b) Seizure susceptibility after depletion of spinal or cerebellar noradrenaline with 6-OHDA. Brain Res 166:418–421
Maynert EW, Marczynski TJ, Browning RA (1975) The role of the neurotransmitters in the epilepsies. Adv Neurol 13:79–147
Menkes DB, Baraban JM, Aghajanian GK (1981) Prazosin selectively antagonizes neuronal responses mediated by α2-adrenoceptors in brain. Naunyn-Schmiedeberg's Arch Pharmacol 317:273–275
Moroni F, Bianchi C, Moneti G, Tanganelli S, Spidalieri G, Guandalini P, Beani L (1982) Release of GABA from the guinea-pig neocortex induced by electrical stimulation of the ‘locus coeruleus’ or by norepinephrine. Brain Res 232:216–221
Murmann W, Almirante L, Saccani-Guelfi M (1966) Central nervous system effects of four β-adrenergic receptor blocking agents. J Pharm Pharmacol 18:317–318
Papanicolaou J, Summers RJ, Vajda FJE, Louis WJ (1982a) Anticonvulsant effects of clonidine mediated through central α2-adrenoceptors. Eur J Pharmacol 77:163–166
Papanicolaou J, Vajda FJE, Summers RJ, Louis WJ (1982b) Role of β-adrenoceptors in the anticonvulsant effect of propanolol on leptazol-induced convulsions in rats. J Pharm Pharmacol 34:124–125
Ponzio F, Jonsson S (1979) A rapid and simple method for the determination of picogram levels of serotonin in brain tissue using liquid chromatography with electrochemical detection. J Neurochem 32:129–132
Quattrone A, Crunelli V, Samanin R (1978) Seizure susceptibility and anticonvulsant activity of carbamazepine, diphenylhydantoin and phenobarbital in rats with selective depletions of brain monoamines. Neuropharmacology 17:643–647
Rochette L, Bralet AM, Bralet J (1974) Influence de la clonidine et la liberation de la noradrénaline dans différentes structures cérébrales du rat. J Pharmacol (Paris) 5:209–220
Rodriguez R, Rojas-Ramirez JA, Drucker-Colin RR (1973) Serotonin-like actions of quipazine on the central neryous system. Eur J Pharmacol 24:164–171
Roussinov KS, Lazarova MB, Yanev SG (1975) On some correlations between adrenergic and serotonergic mechanisms of convulsive-seizure reactivity. Pol J Pharmacol Pharm 27 suppl:231–235
Roussinov KS, Lazarova MB, Atanassova-Shopova S (1976) On certain relationships between gamma-aminobutyric acid (GABA) and adrenergic mechanisms in convulsive seizure reactions. Acta Physiol Pharmacol Bulg 2:69–75
Samanin R, Jori A, Bernasconi S, Morpurgo E, Garattini S (1977 a) Biochemical and pharmacological studies on amineptine (S 1694) and (+)-amphetamine in the rat. J Pharm Pharmacol 29:555–558
Samanin R, Bendotti C, Miranda F, Garattini S (1977 b) Decrease of food intake by quipazine in the rat: Relation to serotonergic receptor stimulation. J Pharm Pharmacol 29:53–54
Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F, Garattini S (1979) m-Chlorophenylpiperazine: A central serotonin agonist causing powerful anorexia in rats. Naunyn-Schmiedeberg's Arch Pharmacol 308:159–163
Schmutz M, Olpe H-R, Koella WP (1979) Central actions of valproate sodium. J Pharm Pharmacol 31:413–414
Simon D, Penry JK (1975) Sodium di-N-propylacetate (DPA) in the treatment of epilepsy. Epilepsia 16:549–573
Snyder SH, Goodman RR (1980) Multiple neurotransmitter receptors. J Neurochem 35:5–15
Stone WE, Javid MJ (1979) Quantitative evaluation of the actions of anticonvulsants against different chemical convulsants. Arch Int Pharmacodyn Ther 240:66–78
Suenaga N, Yamada K, Fukuda T (1977) Correlation between central catecholamine level and post-decapitation convulsion in rats treated with 6-hydroxydopamine. Brain Res 122:165–169
Svensson TH, Bunney BS, Aghajanian GK (1975) Inhibition of both noradrenergic and serotonergic neurons in brain by the α-adrenergic agonist clonidine. Brain Res 92:291–306
U'Prichard DC, Greenberg DA, Snyder SH (1977) Binding characteristics of a radiolabeled agonist and antagonist at central nervous system alpha noradrenergic receptors. Mol Pharmacol 13:454–473
U'Prichard DC, Bechtel WD, Rouot BM, Snyder SH (1979) Multiple apparent alpha-noradrenergic receptor binding sites in rat brain: Effect of 6-hydroxydopamine. Mol Pharmacol 16:47–60
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Lazarova, M., Bendotti, C. & Samanin, R. The role of different types of adrenergic receptors in phentylenetetrazol-induced seizures and the effect of di-n-propylacetate in the rat. Psychopharmacology 81, 177–182 (1983). https://doi.org/10.1007/BF00429015
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DOI: https://doi.org/10.1007/BF00429015