Skip to main content
SpringerLink
Log in

Aspirin Curtails the Acetaminophen-Induced Rise in Brain Norepinephrine Levels

  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

We previously showed that acetaminophen administration to rats increases forebrain serotonin levels as a result of the inhibition of liver tryptophan-2,3-dioxygenase (TDO). In this study we determined whether aspirin alone and in combination with acetaminophen could further influence brain serotonin as well as norepinephrine levels and if so whether the status of the liver TDO activity would be altered. The results show that acetaminophen alone increases brain serotonin as well as norepinephrine levels with a concomitant inhibition of liver TDO activity. In contrast, aspirin did not alter the levels of these monoamines but increased serotonin turnover in the brain while acetaminophen decreased the turnover. When combined with acetaminophen, aspirin overrides the reduced serotonin turnover induced by acetaminophen. This report demonstrates the potential of these agents to alter neurotransmitter levels in the brain.

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

  • Abbot, F.V., and Fraser, M.I. (1998). Use and abuse of over-the-counter analgesic agents. J. Psychiatry Neurosci. 23:13-34.

    Google Scholar 

  • Badawy, A.A.B. (1979). Central role of tryptophan pyrrolase in haem metabolism. Biochem. Soc. Trans. 7:575-583.

    Google Scholar 

  • Badawy, A.A.B., and Evans, M. (1975). Regulation of rat liver tryptophan pyrrolase by its cofactor haem: Experiments with haematin and 5-aminolaevulinate and comparison with the substrate and hormonal mechanisms. Biochem. J. 150:511-520.

    Google Scholar 

  • Badawy, A.A.B., Welch, N., and Morgan, C.J. (1981). Tryptophan pyrrolase in haem regulation. The mechanism of the opposite effects of tryptophan on rat liver 5-aminolaevulinate synthase activity and the haem saturation of tryptophan pyrrolase. Biochem. J. 198:309-314.

    Google Scholar 

  • Carlsson, A., and Lindqvist, M. (1978). Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino-acids in rat brain. Naunyn Schmiedebergs Arch. Pharmakol. 303:157-164.

    Google Scholar 

  • Charney, D.S. (1998). Monoamine dysfunction and the pathophysiology and treatment of depression. J. Clin. Psychiatry 59:11-14.

    Google Scholar 

  • Courade, J.P., Caussade, F., Martin, K., Besse, D., Delchambre, C., and Hanoun, N. (2000). Effects of acetaminophen on monoaminergic systems in the rat central nervous system. Naunyn Schmiedebergs Arch. Pharmakol. 364:534-537.

    Google Scholar 

  • Daya, S., and Anoopkumar-Dukie, S. (2000). Acetaminophen inhibits liver tryptophan-2, 3-dioxygenase activity with a concomitant rise in brain serotonin levels and a reduction in urinary 5-hydroxyindoleacetic acid. Life Sci. 67:235-240.

    Google Scholar 

  • Daya, S., Nonaka, K.O., Buzzel, G.R., and Reiter, R.J. (1989). Heme precursor 5-aminolevulinic acid alters brain tryptophan and serotonin lelves without changing pineal serotonin and melatonin concentrations. J. Neurosci. Res. 23:304-309.

    Google Scholar 

  • Elkind, A.H. (1991). Drug abuse and headache. Med. Clin. N. Am. 75:717-732.

    Google Scholar 

  • Fernstrom, J.D., and Wurtman, R.J. (1971). Brain serotonin content: Physiological dependence on plasma tryptophan levels. Science 173:149-152.

    Google Scholar 

  • Greengard, O., and Feigelson, P. (1960). The activation and induction of rat liver tryptophan pyrrolase in vivo by its substrate. J. Biol. Chem. 236:158-161.

    Google Scholar 

  • Hardeland, R., and Rensing, L. (1968). Circadian oscillation in rat liver tryptophan pyrrolase and its analysis by substrate and hormone induction. Nature 219:619-621.

    Google Scholar 

  • Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951). Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265-267.

    Google Scholar 

  • Mohanakumar, K.P., Mohanty, S., and Ganguly, D.K. (1995). Single neonatal administration of serotonin antiserum inhibits serotonin metabolism and function in adult rats. Neuroreport 7:238-240.

    Google Scholar 

  • Muralikrishnan, D., and Mohanakumar, K.P. (1998). Neuroprotection by bromocriptine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced neurotoxicity in mice. FASEB J. 12:905-912.

    Google Scholar 

  • Seifert, C.F., Lucas, D.S., Vondracek, T.G., Kastens, D.J., McCarthy, D.L., and Bui, B. (1993). Patterns of acetaminophen use in alcoholic patients. Pharmacotherapy 13:391-395.

    Google Scholar 

  • Walsh, H.A., and Daya, S. (1998). Influence of the antidepressants desipramine and fluoxetine on tryptophan-2,3-dioxygenase in the presence of exogenous melatonin. Life Sci. 62:2417-2423.

    Google Scholar 

  • Xi-Ming Li, S., Perry, K.W., and Wong, D.T. (2002). Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentrations in three mesocorticolimbic areas of rats. Neuropharmacology 42:181-190.

    Google Scholar 

  • Zar, J.H. (1974). Biostatistical Analysis, Prentice Hall, Englewood Cliffs, NJ.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pharmacology, Department of Pharmacy, Rhodes University, Grahamstown, South Africa

    Himant Maharaj, Deepa S. Maharaj & Santy Daya

  2. Division of Neurosciences, Indian Institute of Chemical Biology 4, Calcutta, India

    Karruppagounder S. Saravanan & Kochupurackal P. Mohanakumar

Authors
  1. Himant Maharaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deepa S. Maharaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karruppagounder S. Saravanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kochupurackal P. Mohanakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Santy Daya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Santy Daya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maharaj, H., Maharaj, D.S., Saravanan, K.S. et al. Aspirin Curtails the Acetaminophen-Induced Rise in Brain Norepinephrine Levels. Metab Brain Dis 19, 71–77 (2004). https://doi.org/10.1023/B:MEBR.0000027418.33772.8b

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MEBR.0000027418.33772.8b

Search

Navigation