Skip to main content

Advertisement

SpringerLink
Log in

The Effect of Curcumin on Ethanol Induced Changes in Suprachiasmatic Nucleus (SCN) and Pineal

  • Original Paper
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

(1) Circadian clocks have been localized to discrete sites within the nervous system of several organisms and in mammals to the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN controls and regulates the production and discharge of melatonin (hormonal message of darkness) from the pineal gland via a multisynaptic efferent pathway. The nocturnal rise in melatonin production from serotonin results due to an increased activity of serotonin N-acetyl transferase (NAT). (2) The complex interaction between alcohol and biological clock need to be understood as alcoholism results in various clock linked neuronal disorders especially loss of memory and amnesia like state of consciousness, sleep disorders, insomnia, dementia etc. (3) Serotonin, 5-Hydroxy-tryptamine (5-HT) plays an important role in mediating alcohol’s effects on the brain. Understanding the impact of alcohol consumption on circadian system is a pre-requisite to help in treatment of alcohol induced neurological disorders. We, therefore, studied the effect of ethanol drinking and ethanol withdrawal on daily rhythms of serotonin and its metabolite, 5-hydroxy-indole acetic acid (5-HIAA) in SCN and Pineal of adult male Wistar rats maintained under light-dark (LD, 12:12) conditions. (4) Curcumin is well known for its protective properties such as antioxidant, anti-carcinogenic, anti-viral and anti-infectious etc. Hence, we studied the effect of curcumin on ethanol induced changes on 5-HT and 5-HIAA levels and rhythms in SCN and Pineal. (5) Ethanol withdrawal could not restore either rhythmicity or phases or levels of 5-HT and 5-HIAA. Curcumin administration resulted in partial restoration of daily 5-HT/5-HIAA ratio, with phase shifts in SCN and in Pineal. Understanding the impact of alcohol consumption on circadian system and the role of herbal medication on alcohol withdrawal will help in treatment of alcohol induced neurological disorders.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:363–398

    PubMed  CAS  Google Scholar 

  • Arajuo CC, Leon LL (2001) Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 96:723–728

    Google Scholar 

  • Baird TJ, Briscoe RJ, Vallett M, Vanecek SA, Holloway FA, Gauvin DV (1998) Phase–response curve for ethanol: alterations in circadian rhythms of temperature and activity in rats. Pharmacol Biochem Behav 61:303–315

    Article  PubMed  CAS  Google Scholar 

  • Barr SI (1988) Influence of increasing concentrations of ethanol on food and water intake, body weight and wheel running activity of male Sprague-Dawley rats. Pharmacol Biochem Behav 29:667–673

    Article  PubMed  CAS  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Carmichael FJ, Israel Y (1975) Effects of ethanol on neurotransmitter release by rat brain cortical slices. J Pharmacol Exp Ther 193:824–834

    PubMed  CAS  Google Scholar 

  • Chen CP, Kuhn P, Advis JP, Sarkar DK (2004) Chronic ethanol consumption impairs the circadian rhythm of pro-opiomelanocortin and period genes mRNA expression in the hypothalamus of the male rat. J Neurochem 88:1547–1554

    Article  PubMed  CAS  Google Scholar 

  • Dahchour A, Quertemont E, De Witte P (1994) Acute ethanol increases taurine but neither glutamate nor GABA in the nucleus accumbens of male rats: a micro dialysis study. Alcohol Alcohol 29:485–487

    PubMed  CAS  Google Scholar 

  • Danel T, Touiton Y (2006) Alcohol consumption does not effect melatonin circadian synchronization in healthy men. Alcohol Alcohol 41:386–390

    PubMed  CAS  Google Scholar 

  • Ehlers CL, Slawecki CJ (2000) Effects of chronic ethanol exposure on sleep in rats. Alcohol 20:173–179

    Article  PubMed  CAS  Google Scholar 

  • El-Mas MM, Abdel-Rahman AA (2000) Radio telemetric evaluation of homodynamic effects of long-term ethanol in spontaneously hypertensive and Wistar-Kyoto rats. J Pharmacol Exp Therapeut 292:944–951

    CAS  Google Scholar 

  • Fonzi S, Solinas GP, Costelli P, Parodi C, Murialdo G, Bo P, Albergati A, Montalbetti L, Savoldi F, Polleri A (1994) Melatonin and cortisol circadian secretion during ethanol withdrawal in chronic alcoholics. Chronobiologia 21:109–112

    PubMed  CAS  Google Scholar 

  • Gewiss M, Heidbreder C, Opsomer L, Durbin P, De Witte P (1991) Acamprosate and diazepam differentially modulate alcohol-induced behavioral and cortical alterations in rats following chronic inhalation of ethanol vapor. Alcohol Alcohol 26:129–137

    PubMed  CAS  Google Scholar 

  • Glue P, Nutt D (1990) Overexcitement and disinhibition. Dynamic neurotransmitter interactions in alcohol withdrawal. Br J Psychiatry 157:491–499

    PubMed  CAS  Google Scholar 

  • Grady RK, Caliguri JA, Mefford IN (1984) Day/night differences in pineal indoles in the adult pigeon (Columba livia). Comp Biochem Physiol 78:141–143

    Google Scholar 

  • Grant KA, Valverius P, Hudspith M, Tabakoff B (1990) Ethanol withdrawal seizures & the NMDA receptor complex. Eur J Pharmacol 176:289–296

    Article  PubMed  CAS  Google Scholar 

  • Imatoh N, Nakazawa Y, Ohshima H, Ishibashi M, Yokoyama T (1986) Circadian rhythm of REM sleep of chronic alcoholics during alcohol withdrawal. Drug Alcohol Depend 18:77–85

    Article  PubMed  CAS  Google Scholar 

  • Iranmanesh A, Veldhuis JD, Johnson ML, Lizarralde G (1989) 24-hour pulsatile and circadian patterns of cortisol secretion in alcoholic men. J Androl 10:54–63

    PubMed  CAS  Google Scholar 

  • Jagota A (2005) Aging and sleep disorders. Indian J Gerontol 19:415–424

    Google Scholar 

  • Jagota A (2006) Suprachiasmatic nucleus: the center for circadian timing system in mammals. Proc Indian Natl Sci Acad B71:275–288

    Google Scholar 

  • Jagota A, de la Iglesia HO, Schwartz WJ (2000) Morning and evening circadian oscillations in the suprachiasmatic nucleus in vitro. Nat Neurosci 3:372–376

    Article  PubMed  CAS  Google Scholar 

  • Joe B, Vijay Kumar M, Lokesh BR (2004) Biological properties of curcumin – cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 44:97–111

    Article  PubMed  CAS  Google Scholar 

  • Kawahara F, Saito H, Katsuki H (1993) Pharmacological characteristics of GABAa responses in post natal suprachiasmatic neurons in culture. Neurosci Lett 160:45–48

    Article  PubMed  CAS  Google Scholar 

  • Klein DC, Coon SL, Roseboom PH, Weller JL, Bernard M, Gastel JA, Zatz M, Iuvone PM, Rodriguez IR, Bégay V, Falcón J, Cahill GM, Cassone VM, Baler R (1997) The melatonin rhythm generating enzyme: molecular regulation of serotonin N-acetyl transferase in the pineal gland. Recent Prog Horm Res 52:307–358

    PubMed  CAS  Google Scholar 

  • Klein DC, Moore RY, Reppert SM (1991) Suprachiasmatic nucleus: the mind’s clock. Oxford University Press, New York

    Google Scholar 

  • Kodama H, Nakazawa Y, Kotorii T, Nonaka K, Inanaga K, Ohshima M, Tokoyama T (1988) Biorhythm of core temperature in depressive and non-depressive alcoholics. Drug Alcohol Depend 21:1–6

    Article  PubMed  CAS  Google Scholar 

  • LeMarquand D, Pihl RO, Benkelfat C (1994) Serotonin and alcohol intake, abuse, and dependence: findings of animal studies. Biol Psychiatry 36:395–421

    Article  PubMed  CAS  Google Scholar 

  • Littleton J (1998) Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health Res World 22:13–24

    PubMed  CAS  Google Scholar 

  • Lovinger DM (1999) The role of serotonin in alcohol’s effects on the brain. Curr Sep 18:23–28

    CAS  Google Scholar 

  • Madeira MD, Paul-Barbosa MM (1999) Effect of alcohol on the synthesis and expression of hypothalamic peptides. Brain Res Bull 48:3–22

    Article  PubMed  CAS  Google Scholar 

  • Mefford IN, Chang P, Klein DC, Namboodiri MAA, Sugden D, Barchas J (1980) Determination of tryptophan and metabolites in rat brain and pineal tissue by reversed-phase high-performance liquid chromatography with electrochemical detection. J Chromatogr 181:187–193

    Article  PubMed  CAS  Google Scholar 

  • Michaelis EK, Mulvaney MJ, Freed WJ (1978) Effects of acute and chronic ethanol intake on synaptosomal lutamate binding activity. Biochem Pharmacol 27:1685–1691

    Article  PubMed  CAS  Google Scholar 

  • Mistleberger RE, Nadeau J (1992) Ethanol and circadian rhythms in Syrian hamster: effects on entrained phase, reentrainment rate and period. Pharmacol Biochem Behav 43:159–165

    Article  Google Scholar 

  • Mistleberger RE, Antle MC, Glass JD, Miller JD (2000) Behavioral and serotonergic regulation of circadian rhythms. Biol Rhythm Res 31:240–283

    Article  Google Scholar 

  • Moore RY (1991) Suprachiasmatic nucleus. In: Klein DC, Moore RY, Reppert SM (eds) Disorders of circadian function and the human circadian timing system. Oxford University Press, New York, pp 429–441

    Google Scholar 

  • Morin LP (1999) Serotonin and the regulation of mammalian circadian rhythmicity. Ann Med 31:12–33

    PubMed  CAS  Google Scholar 

  • Moyer RW, Kennaway DJ (1999) Immunohistochemical localization of serotonin receptors in the rat suprachiasmatic nucleus. Neurosci Lett 271:147–150

    Article  PubMed  CAS  Google Scholar 

  • Mukai M, Uchimura N, Hirano T, Ohshima H, Ohshima M, Nakamura J (1998) Circadian rhythms of hormone concentration in alcohol withdrawal. Psychiatry Clin Neurosci 52:238–240

    Article  PubMed  CAS  Google Scholar 

  • Oncken C, Van Kirk J, Kranzler HR (2001) Adverse effects of oral naltrexone: analysis of data from two clinical trials. Psychopharmacology 154:397–402

    Article  PubMed  CAS  Google Scholar 

  • Oscar MA, Bataillon C, Bagheri H, Le Quellec A, Rolland F, Montastruc JL (2003) Acamprosate (Aotal): could adverse effects upset the treatment of alcohol dependence? Therapie 58:371–374

    Article  PubMed  Google Scholar 

  • Petrakis I, Krystal J (1997) Neuroscience implications for treatment. Alcohol Health Res world 21:177–179

    Google Scholar 

  • Prospero G, Criado JR, Henriksen SJ (1994) Pharmacology of ethanol and glutamate antagonists on rodent sleep. A comparative study. Pharmacol Biochem Behav 49:413–416

    Article  Google Scholar 

  • Prosser RA, Gillette MU (1989) The mammalian circadian clock in the suprachiasmatic nuclei is reset in vitro by cAMP. J Neurosci 9:1073–1081

    PubMed  CAS  Google Scholar 

  • Rajakrishnan V, Subramanian P, Viswanathan P, Menon VP (1999) Effect of chronic ethanol ingestion on biochemical circadian rhythms in Wistar rats. Alcohol 18:147–152

    Article  PubMed  CAS  Google Scholar 

  • Rea MA, Pickard GE (2000) Serotonergic modulation of the photic entrainment in the Syrian hamster. Biol Rhythm Res 31:284–314

    Article  CAS  Google Scholar 

  • Sano H, Suzuki Y, Yazaki R, Tamefusa K, Ohara K, Yokoyama T, Miyasato K, Ohara K (1993) Circadian variation in plasma 5-HIAA level during and after alcohol withdrawal. Acta Psychiatr Scand 87:291–296

    Article  PubMed  CAS  Google Scholar 

  • Sano H, Suzuki Y, Ohara K, Miyasato K, Yokoyama T, Ohara K (1994) Circadian variations in plasma monoamine metabolites level in alcoholic patients: a possible predictor of alcohol withdrawal delirium. Prog Neuro-psychopharmacol Biol Psychiatry 18:741–752

    Article  CAS  Google Scholar 

  • Spanagel R, Rosenwasser AM, Shumann G, Sarkar DK (2005) Alcohol consumption and the body’s clock. Alcohol Clin Exp Res 29:1550–1557

    Article  PubMed  Google Scholar 

  • Tabakoff B, Hoffman PL (1996) Alcohol addiction: an enigma among us. Neuron 16:909–912

    Article  PubMed  CAS  Google Scholar 

  • Valenuzuela CF, Harris RA (1997) Alcohol: neurobiology. In: Lowinson JH, Ruiz P, Millman RB, Langrod JG (eds) Substance abuse: a comprehensive textbook. Williams & Wilkins, Baltimore, pp 112–142

  • Verge C, Lucena MI, López-Torres E, Puche-Garcia MJ, Fraga E, Romero-Gomez M, Andrade RJ (2006) Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: is there still a role for these drugs? World J Gastroenterol 12:5078–5080

    PubMed  CAS  Google Scholar 

  • Yoshimoto K, McBride WJ, Lumeng L, Li TK (1992) Alcohol stimulates the release of dopamine and serotonin in the nucleus accumbens. Alcohol 9:17–22

    Article  PubMed  CAS  Google Scholar 

  • Zarcone V (1978) Alcoholism and sleep. Adv Biosci 21:29–38

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work supported by research grants from ILS (EFL/II/CS-MoU/112/1872 dt. 14.12.2004) and DST (Do No: SR/SO/AS-47/2004) to A.J. CSIR fellowship to M.Y. Reddy is acknowledged.

Author information

Authors and Affiliations

  1. Neurobiology and Molecular Chronobiology Laboratory, Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India

    Anita Jagota & M. Y. Reddy

Authors
  1. Anita Jagota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Y. Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anita Jagota.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jagota, A., Reddy, M.Y. The Effect of Curcumin on Ethanol Induced Changes in Suprachiasmatic Nucleus (SCN) and Pineal. Cell Mol Neurobiol 27, 997–1006 (2007). https://doi.org/10.1007/s10571-007-9203-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-007-9203-8

Keywords

Search

Navigation