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Caffeine augmentation of electroconvulsive seizures

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Abstract

Caffeine has been used clinically to increase seizure length in electroconvulsive treatment (ECT). The present study was designed to establish an animal model of caffeine-augmented seizures for further study of mechanisms and effects of pharmacological manipulation of seizure length. Increasing doses of caffeine (0–200 mg/kg, IP) were given before electroconvulsive stimulation (ECS) in rats and resulting seizure lengths were quantified by timing of classical tonic-clonic convulsive movements. With this paradigm, caffeine led to a dose-dependent increase in seizure duration. This proconvulsant action of caffeine was detectable within 1 min after dosing, persisted for at least 230 min and was reversible. The results suggest that seizure length is a practicable measure in pharmacological modification of electroconvulsive seizures. They also suggest that pharmacologically-modified ECS can be modeled effectively in animals.

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References

  • Abrams R (1988) Electroconvulsive therapy. Oxford University Press, New York

    Google Scholar 

  • Albertson TE, Joy RM, Stark LG (1983) Caffeine modification of kindled amygdaloid seizures. Pharmacol Biochem Behav 19:339–343

    Article  PubMed  Google Scholar 

  • Ameri A, Jurna I (1991) Adenosine A1 and non-A1 receptors: intracellular analysis of the actions of adenosine agonists and antagonists in rat hippocampal neurones. Brain Res 546:69–78

    Article  PubMed  Google Scholar 

  • American Psychiatric Association (1990) The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging. APA Press, Washington, DC

    Google Scholar 

  • Ault B, Wang CM (1986) Adenosine inhibits epileptiform activity arising in hippocampal area CA3. Br J Pharmacol 87:695–703

    PubMed  Google Scholar 

  • Ault B, Olney MA, Joyner JL, Boyer CE, Notrica MA, Soroko, Wang CM (1987) Pro-convulsant actions of theophylline and caffeine in the hippocampus: implications for the management of temporal lobe epilepsy. Brain Res 426:93–102

    Article  PubMed  Google Scholar 

  • Bonati M, Garattini S (1984) Interspecies comparisons of caffeine disposition. In: Dews PB (ed) Caffeine: perspectives from recent research. Springer, Berlin, pp 48–56

    Google Scholar 

  • Bonati M, Latini R, Tognoni G, Young JF, Garattini S (1984–85) Interspecies comparison of in vivo caffeine pharmacokinetics in man, monkey, rabbit, rat, and mouse. Drug Metab Rev. 15:1355–1383

    PubMed  Google Scholar 

  • Bortolotti A, Traina GL, Guaitani A, Marzi E, Latini R, Young JF, Bonati M (1990) In vivo and perfused liver caffeine kinetics in the rat. Res Commun Chem. Pathol Pharmacol 69:285–295

    PubMed  Google Scholar 

  • Bowery NG, Hudson AL, Price GW (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20:365–383

    PubMed  Google Scholar 

  • Cantú TG, Korek JS (1991) Caffeine in electroconvulsive therapy. DICP 25:1079–1080

    PubMed  Google Scholar 

  • Chen G, Ensor CR, Bohner B (1968) Studies of drug effects on electrically induced extensor seizures and clinical implications. Arch Int Pharmacodyn 172:183–218

    PubMed  Google Scholar 

  • Choi OH, Shamim MT, Padgett WL, Daly JW (1988) Caffeine and theophylline analogues: correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors. Life Sci 43:387–398

    PubMed  Google Scholar 

  • Chu NS (1981) Caffeine- and aminophylline-induced seizures. Epilepsia 22:85–94

    PubMed  Google Scholar 

  • Coffey CE, Figiel GS, Weiner RD, Saunders WB (1990) Caffeine augmentation of ECT. Am J Psychiatry 147:579–585

    PubMed  Google Scholar 

  • Cutrufo C, Bortot L, Giachetti A, Manzini S (1992) Differential effects of various xanthines on pentylenetetrazole-induced seizures in rats: an EEG and behavioural study. Eur J Pharmacol 222:1–6

    PubMed  Google Scholar 

  • Daly JW, Hide I, Müller CE, Shamim M (1991) Caffeine analogs: structure-activity relationships at adenosine receptors. Pharmacology 42:309–321

    PubMed  Google Scholar 

  • Dragunow M, Robertson HA (1987) 8-Cyclopentyl-1,3-dimethylxanthine prolongs epileptic seizures in rats. Brain Res 417:377–379

    PubMed  Google Scholar 

  • Dunwiddie TV (1980) Endogenously released adenosine regulates excitability in the in vitro hippocampus. Epilepsia 21:541–548

    PubMed  Google Scholar 

  • Dunwiddie TV, Fredholm BB (1984) Adenosine receptors mediating inhibitory electrophysiological responses in rat hippocampus are different from receptors mediating cyclic AMP accumulation. Naunyn-Schmiedeberg's Arch Pharmacol 326:294–301

    Google Scholar 

  • Evoniuk G, Von Borstel RW, Wurtman RJ (1987) Antagonism of the cardiovascular effects of adenosine by caffeine or 8-(p-sulfophenyl)-theophylline. J Pharmacol Exp Ther 240:428–432

    PubMed  Google Scholar 

  • Fastbom J, Pazos A, Palacios JM (1987) The distribution of adenosine A1 receptors and 5′-nucleotidase in the brain of some commonly used experimental animals. Neuroscience 22:813–826

    PubMed  Google Scholar 

  • File SE, Baldwin HA, Johnston AL, Wilks LJ (1988) Behavioral effects of acute and chronic administration of caffeine in the rat. Pharmacol Biochem Behav 30:809–815

    Article  PubMed  Google Scholar 

  • Foote WE, Holmes P, Pritchard A, Hatcher C, Mordes J (1978) Neurophysiological and pharmacodynamic studies on caffeine and on interactions between caffeine and nicotinic acid in the rat. Neuropharmacolgy 17:7–12

    Google Scholar 

  • Francis A, Fochtmann L (1993) Pharmacological augmentation of ECS: neurochemistry. Convulsive Ther 9:77

    Google Scholar 

  • Fredholm BB (1985) On the mechanism of action of theophylline and caffeine. Acta Med Scand 217:149–53

    PubMed  Google Scholar 

  • Garattini S (1985) Active drug metabolites: an overview of their relevance in clinical pharmacokinetics. Clin Pharmacokinet 10:216–227

    PubMed  Google Scholar 

  • Jarvis MF, Jacobson KA, Williams M (1987) Autoradiographic localization of adenosine A1 receptors in rat brain using [3H]XCC, a functionalized congener of 1,3-dipropylxanthine. Neurosci Lett 81:69–74

    PubMed  Google Scholar 

  • Jarvis MF, Jackson RH, Williams M (1989) Autoradiographic characterization of high-affinity adenosine A2 receptors in rat brain. Brain Res 484:111–118

    PubMed  Google Scholar 

  • Khanna KL, Rao GS, Cornish HH (1972) Metabolism of caffeine-3H in the rat. Toxicol Appl Pharmacol 23:720–730

    PubMed  Google Scholar 

  • Latini R, Bonati M, Castelli D, Garattini S (1978) Dose-dependent kinetics of caffeine in rats. Toxicol Lett 2:267–270

    Article  Google Scholar 

  • Lee KS, Reddington M (1986) Autoradiographic evidence for multiple CNS binding sites for adenosine derivatives. Neuroscience 19:535–549

    PubMed  Google Scholar 

  • Marangos PJ, Paul SM, Parma AM, Goodwin FK, Syapin P, Skolnick P (1979) Purinergic inhibition of diazepam binding to rat brain (in vitro). Life Sci 24:851–858

    Article  PubMed  Google Scholar 

  • McPherson PS, Kim Y-K, Valdivia H, Knudson CM, Takekura H, Franzini-Armstrong, C, Coronado R, Campbell KP (1991) The brain ryanodine receptor: a caffeine-sensitive calcium release channels. Neuron 7:17–25

    PubMed  Google Scholar 

  • Modrow HE, Holloway FA, Christensen HD, Carney JM (1981) Relationship between caffeine discrimination and caffeine plasma levels. Pharmacol Biochem Behav 15:323–325

    PubMed  Google Scholar 

  • Nehlig A, Daval J-L, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Rev 17:139–170

    Article  Google Scholar 

  • Sackeim H, Decina P, Prohovnik I, Malitz S (1987) Seizure threshold in electroconvulsive therapy. Arch Gen Psychiatry 44:355–360

    PubMed  Google Scholar 

  • Sant'Ambrogio G, Mognoni P, Ventrella L (1964) Plasma levels of caffeine after oral, intramuscular and intravenous administration. Arch Int Pharmcodyn 150:259–263

    Google Scholar 

  • Sattin A (1971) Increase in the content of adenosine 3′,5′-monophosphate in mouse forebrain during seizures and prevention of the increase by methylxanthines. J Neurochem 18:1087–1096

    PubMed  Google Scholar 

  • Sawynok J, Yaksh T (1993) Caffeine as an analgesic adjuvant: a review of pharmacology and mechanisms of action. Pharmacol Rev 45:43–85

    PubMed  Google Scholar 

  • Shapira B, Lerer B, Gilboa D, Drexler H, Kugelmass S, Calev A (1987) Facilitation of ECT by caffeine pretreatment. Am J Psychiatry 144:1199–1202

    PubMed  Google Scholar 

  • Ståhle L, Segersvärd S, Ungerstedt U (1991) Drug distribution studies with microdialysis: II. Caffeine and theophylline in blood, brain and other tissues in rats. Life Sci 49:1843–1852

    PubMed  Google Scholar 

  • Swartz CM, Lewis RK (1991) Theophylline reversal of electroconvulsive therapy (ECT) seizure inhabition. Psychosomatics 32:47–51

    PubMed  Google Scholar 

  • Tanaka E, Ishikawa A, Yamamoto Y, Uchida E, Kobayashi S, Yasuhara H, Misawa S (1992) Simplified approach for evaluation of hepatic drug-oxidizing capacity with a simultaneous measurement of caffeine and its primary demethylated metabolites in carbon tetrachloride-intoxicated rats. Xenobiotica 22:535–541

    PubMed  Google Scholar 

  • Thithapandha A, Maling HM, Gillette JR (1972) Effects of caffeine and theophylline on activity of rats in relation to brain xanthine concentrations. Proc Soc Exp Biol Med 139:582–586

    PubMed  Google Scholar 

  • Thompson SM, Haas HL, Gähwiler BH (1992) Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampus in vitro. J Physiol 451:347–363

    PubMed  Google Scholar 

  • Torres IJ, Litterst CL, Guarino AM (1978) Transport of model compounds across the peritoneal membrane in the rat. Pharmacology 17:330–340

    PubMed  Google Scholar 

  • Tsuzuki J, Newburgh RW (1975) Inhibition of 5′-nucleotidase in rat brain by methylxanthines. J Neurochem 25:895–896

    PubMed  Google Scholar 

  • Weber RG, Jones CR, Lohse MJ, Palacios JM (1990) Autoradiographic visualization of A1 adenosine receptors in rat brain with [3H] 8-cyclopentyl-1,3-dipropylxanthine. J Neurochem 54:1344–1353

    PubMed  Google Scholar 

  • Weir RL, Hruska RE (1983) Interaction between methylxanthines and the benzodiazepine receptor. Arch Int Pharmacodyn 265:42–48

    PubMed  Google Scholar 

  • Yasuhara M, Levy G (1988) Rapid development of functional tolerance to caffeine-induced seizures in rats. Proc Soc Exp Biol Med 188:185–190

    PubMed  Google Scholar 

  • Zhang G, Franklin PH, Murray TF (1993) Manipulation of endogenous adenosine in the rat prepiriform cortex modulates seizure susceptibility. J Pharmacol Exp Ther 264:1415–1424

    PubMed  Google Scholar 

  • Zimanyi I, Pessah IN (1991) Pharmacological characterization of the specific binding of [3H]ryanodine to rat brain microsomal membranes. Brain Res 561:181–191

    PubMed  Google Scholar 

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  1. Department of Psychiatry and Behavioral Sciences, SUNY Stony Brook, 11794, Stony Brook, NY, USA

    Andrew Francis & Laura Fochtmann

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  1. Andrew Francis
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  2. Laura Fochtmann
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Francis, A., Fochtmann, L. Caffeine augmentation of electroconvulsive seizures. Psychopharmacology 115, 320–324 (1994). https://doi.org/10.1007/BF02245072

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  • DOI: https://doi.org/10.1007/BF02245072

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