Skip to main content
SpringerLink
Log in

Reduced proconvulsant activity of caffeine in rats after a series of electroconvulsive seizures

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

A variety of neurotransmitter receptor changes occur after a course of electroconvulsive seizures (ECS) in rats, including an increased density of adenosine A1 sites. Adenosine antagonism has been related to the proconvulsant action of methylxanthines such as caffeine. We determined tonic-clonic seizure duration in rats given ECS with caffeine (0–175 mg/kg, IP) after a course of one or six daily ECS. A single day of ECS did not affect the dose-dependent proconvulsant action of caffeine. After six daily ECS, the proconvulsant action of caffeine was reduced. After nine daily ECS, an A1 antagonist (8-cyclopentyl-1,3-dipropylxanthine) and an A2A antagonist (1-allyl-3,7-dimethyl-8-p-sulfophenylxanthine) showed reduced proconvulsant activity. The results suggest that the reduced proconvulsant action of caffeine after chronic ECS depends on adenosine antagonism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albertson T, Joy R, Stark L (1983) Caffeine modification of kindled amygdaloid seizures. Pharmacol Biochem Behav 19:339–343

    Google Scholar 

  • Angelatou F, Pagonopoulou O, Kostopoulos G (1990) Alterations of A1 adenosine receptors in different mouse brain areas after pentylenetetrazol-induced seizures, but not in the epileptic mutant mouse ‘tottering’. Brain Res 534:251–256

    Google Scholar 

  • Baumgold J, Nikodijevic O, Jacobson K (1992) Penetration of adenosine antagonists into mouse brain as determined by ex vivo binding. Biochem Pharmacol 43:889–894

    Google Scholar 

  • Benowitz N (1990) Clinical pharmacology of caffeine. Annu Rev Med 41:277–288

    Google Scholar 

  • Boulenger J, Patel J, Post R, Parma A, Marangos P (1983) Chronic caffeine consumption increases the number of brain adenosine receptors. Life Sci 32:1135–1142

    Google Scholar 

  • Bruns R, Fergus J, Badger E, Bristol J, Santay L, Hartman J, Hays S, Huang C (1987) Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes. Nauyn-Schmiedeberg Arch Pharmacol 335:59–63

    Google Scholar 

  • Calev A, Fink M, Petrides G, Francis A, Fochtmann L (1993) Caffeine pre-treatment enhances clinical efficacy and reduces cognitive effects of electroconvulsive therapy. Convuls Ther 9:95–100

    Google Scholar 

  • Carney J (1982) Effects of caffeine, theophylline, and theobromide on schedule-controlled responding in rats. Br J Pharm 75:451–454

    Google Scholar 

  • Castanon M, Spevak W (1994) Functional coupling of human adenosine receptors to a ligand-dependent reporter gene system. Biochem Biphys Res Commun 198:626–631

    Google Scholar 

  • Chin J (1988) Adenosine receptors in brain: neuromodulation and role in epilepsy. Ann Neurol 26:69–698

    Google Scholar 

  • Choi O, Shamim M, Padgett W, Daly J (1988) Caffeine and theophylline analogs: correlation with behavcioral erffects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors. Life Sci 43:387–398

    Google Scholar 

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

    Google Scholar 

  • Chweh A, Ulloque R, Swinyard E (1986) Benzodiazepine inhibition of 3H-flunitrazepam binding and caffeine-induced seizures in mice. Eur J Pharmacol 122:161–165

    Google Scholar 

  • Coffey C, Figiel G, Weiner R, Saunders W (1990) Caffeine augmentation of ECT. Am J Psychiatry 147:579–585

    Google Scholar 

  • Daval J-L, Deckert J, Weiss S, Post R, Marangos P (1989) Upregulation of adenosine A1 receptors and forskolin binding sites following chronic treatment with caffeine or carbamazepine: a quantitative autoradiographic study. Epilepsia 301:26–33

    Google Scholar 

  • Dragunow M (1986) Adenosine: the brain's natural anticonvulsant? Trends Pharm Sci 128–130

  • Dunwiddie T, Fredholm B (1989) Adenosine A1 receptors inhibit adenylate cyclase activity and neurotransmitter release and hyperpolarize neurons in rat hippocampus. J Pharmacol Exp Ther 249:31–37

    Google Scholar 

  • During M, Spencer D (1992) Adenosine: a potential mediator of seizure arrest and postictal refractoriness. Ann Neurol 32:618–623

    Google Scholar 

  • Finn I, Holtzman S (1987) Pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity. Psychopharmacology 93:428–434

    Google Scholar 

  • Fochtmann L (1994) Animal studies of electroconvulsive therapy: foundations for future research. Psychopharmacol Bull 30:321–442

    Google Scholar 

  • Francis A, Fochtmann L (1993) Sustained downregulation of cortical beta-adrenergic receptor density with maintenance ECS. Convuls Ther 9:185–191

    Google Scholar 

  • Francis A, Fochtmann L (1994) Caffeine augmentation of electroconvulsive seizures. Psychopharmacology 115:320–324

    Google Scholar 

  • Gleiter C, Nutt D (1989) Minireview: chronic electroconvulsive shock and neurotransmitter receptors: an update. Life Sci 44:985–1006

    Google Scholar 

  • Gleiter C, Deckert J, Nutt D (1988) Changes in caffeine seizure threshold after electroconvulsive shock. Psychopharmacology 95:544–545

    Google Scholar 

  • Gleiter C, Deckert J, Nutt D, Marangos P (1989) Electroconvulsive shock (ECS) and the adenosine neuromodulatory system: effect of single and repeated ECS on the adenosine A1 and A2 receptors, adenylate cyclase, and the adenosine uptake site. J Neurochem 52:641–646

    Google Scholar 

  • Gross R, Ferrendelli J (1979) Effects of reserpine, propranolol, and aminophylline on seizure activity and CNS cyclic nucleotides. Ann Neurol 6:296–301

    Google Scholar 

  • Hawkins M, Dugich M, Porter N, Urbancic M, Radulovacki M (1988) Effects of chronic administration of caffeine on adenosine A1 and A2 receptors in rat brain. Brain Res Bull 21:479–482

    Google Scholar 

  • Holtzman S, Mante S, Minneman K (1991) Role of adenosine receptors in caffeine tolerance. J Pharmacol Exp Ther 256:62–68

    Google Scholar 

  • Jacobson K, Shi D, Gallo-Rodriguez C, Manning M, Muller C, Daly J, Neumeyer J, Kiriasis L, Pfleiderer W (1993) Effect of trifluoromethyl and other substituents on activity of xanthines at adenosine receptors. J Med Chem 36:2639–2644

    Google Scholar 

  • Johansson B, Ahlberg S, Van der Ploeg I, Brene S, Lindefors N, Persson H, Fredholm B (1993) Effect of long term caffeine treatment on A1 and A2 adenosine receptor binding and mRNA levels in rat brain. Nauyn Schmiedeberg Arch Pharmacol 347:404–414

    Google Scholar 

  • Lee K, Schubert P, Heinemann U (1984) The anticonvulsive action of adenosine: a postsynaptic, dendritic action by a possible endogenous anticonvulsant. Brain Res 321:160–164

    Google Scholar 

  • Lerer B, Shapira B, Drexler H, Calev A, Newman M (1986) Pharmacological manipulation of ECT-induced seizure duration. Clin Neuropharmacol 9 ([Suppl 4]):453–455

    Google Scholar 

  • Marangos P, Boulenger J (1985) Basic and clinical aspects of adenosinergic neuromodulation. Neurosci Biobehav Rev 9:421–430

    Google Scholar 

  • Marangos P, Boulenger J, Patel J (1984) Effects of chronic caffeine on brain adenosine receptors: regional and ontogenetic studies. Life Sci 34:899–907

    Google Scholar 

  • Murray T (1982) Upregulation of rat cortical adenosine receptors following chronic administration of theophylline. Eur J Pharmacol 82:113–114

    Google Scholar 

  • Newman M, Zohar J, Kalian M, Belmaker R (1984) The effects of chronic lithium and ECT on A1 and A2 adenosine receptor systems in rat brain. Brain Res 291:188–192

    Google Scholar 

  • Nutt D, Cowen P, Green R (1981) Studies on the post-ictal rise in seizure threshold. Eur J Pharmacol 71:287–295

    Google Scholar 

  • Okada Y, Kuroda Y (1980) Inhibitory action of adenosine and adenosine analogs on neurotransmission in the olfactory cortex slice of guinea pig: structure-activity relationships. Eur J Pharmacol 61:137–146

    Google Scholar 

  • Sanders R, Murray T (1989) Temporal relationship between A1 adenosine receptor upregulation and alterations in bicuculline seizure susceptibility in rats. Neurosci Lett 101:325–330

    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

    Google Scholar 

  • Sattin A (1981) Adenosine as a mediator of antidepressant treatment. In: Rodnight R, et al. Chemisms of the Brain, Churchill-Livingstone, Edinburghff 265–275

    Google Scholar 

  • Seale T, Abla K, Shamim M, Carney J, Daly J (1988) 3,7-Dimethyl-1-propargylxanthine: a potent and selective in vivo antagonist of adenosine analogs. Life Sci 43:1671–1684

    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

    Google Scholar 

  • Shapira B, Zohar J, Newman M, Drexler H, Belmaker R (1985) Potentiation of seizure length and clinical response to electroconvulsive therapy by caffeine pretreatment: a case report. Convuls Ther 1:58–60

    Google Scholar 

  • Snyder S (1985) Adenosine as a neuromodulator. Annu Rev Neurosci 8:103–124, 1985

    Google Scholar 

  • Snyder S, Sklar P (1984) Behavioral and molecular actions of caffeine: focus on adenosine. J Psychiatr Res 18:91–106

    Google Scholar 

  • Szot P, Sanders R, Murray T (1987) Theophylline-induced upregulation of A1-adenosine receptors associated with reduced sensitivity to convulsants. Neuropharmacology 26:1173–1180

    Google Scholar 

  • Wachtel H (1982) Characteristic behavioral alterations in rats induced by rolipram and other selective adenosine cyclic 3′,5′monophosphate phosphodiesterase inhibitors. Psychopharmacology 77:309–316

    Google Scholar 

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

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry Health Sciences Center T-10, SUNY Stony Brook, 11794, Stony Brook, NY, USA

    A. Francis & L. Fochtmann

Authors
  1. A. Francis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Fochtmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Francis, A., Fochtmann, L. Reduced proconvulsant activity of caffeine in rats after a series of electroconvulsive seizures. Psychopharmacology 119, 99–104 (1995). https://doi.org/10.1007/BF02246060

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02246060

Key words

Search

Navigation