Citalopram and Tianeptine: Pharmacological Interventions in alcohol withdrawal-induced negative mood states and serotonin insufficiency in Albino Wistar male rats
The present study aims to investigate the neurochemical and behavioural effects of tianeptine and citalopram to block alcohol withdrawal-induced audiogenic seizures in alcohol withdrawal (AW) rats. Citalopram and tianeptine were administered sub-chronically to block AW-induced audiogenic seizures. Brain regional tryptophan (TRP), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined using high-performance liquid chromatography connected to the fluorimetric detector. Citalopram increased brain TRP concentration in all the regions, however, tianeptine increased brain TRP concentration only in amygdala and hippocampus. Increased brain serotonin concentration was seen by citalopram but not by tianeptine in all the regions. Further, tianeptine was shown to increase 5-HT turnover in all the regions, however, citalopram appeared to increase 5-HT turnover only in the hippocampus. It is concluded that the citalopram and tianeptine behave differently on the intrinsic pathway of serotonin metabolism that appeared to be compensated by the release pattern of serotonin. Further, chronic exposure of serotonergic agents causes restoration and structural reforming of serotonin reuptake mechanism that is desensitized following chronic alcohol exposure. Thus the inclusive approach of the serotonergic system plays an undoubted role in the pharmacological management of AW syndrome.
Anderson G.M., Young J.G. Batter D.K, Young S.N., Cohen D.J., Shaywitz B. A., 1981. Determination of indoles and catechols in rat brain and pineal using liquid chromatography with fluorometric and amperometric detection J Chromatogr 223(2): 315-20.
Ara I, Bano S., 2012. Citalopram decreases tryptophan 2, 3 dioxygenase activity and brain 5-HT turnover in swim stressed rats Pharmacol Rep 64(3):558-66.
Ara I1, Bano S1., 2015. Serotonergic activity and hypothalamic-pituitary-adrenal axis response in alcohol administered and subsequently withdrawn rats Pak J Pharm Sci. 28(4):1259-65.
Badawy A.A, Aliyu SU., 1984. Antagonism of acute alcohol intoxication by naloxone Alcohol Alcohol.19(3):199-201.
Badawy AA1., 2002. Tryptophan metabolism in alcoholism. Nutr Res Rev. 15(1):123-52. doi: 10.1079/NRR200133.
Badawy AA1., 2013. Tryptophan: the key to boosting brain serotonin synthesis in depressive illness. J Psychopharmacol. 27(10):878-93.
Balldin J1., Berggren U, Engel J, Eriksson M, Hård E, Söderpalm B.1994 Effect of citalopram on alcohol intake in heavy drinkers. Alcohol Clin Exp Res. 1994. 18(5):1133-6.
Banerjee N., 2014.Neurotransmitters in alcoholism: A review of neurobiological and genetic studies. Ind J Hum Genet 20 (1): 20-31
Bano S, Gitay M, Ara I, Badawy A., 2010 Acute effects of serotonergic antidepressants on tryptophan metabolism and corticosterone levels in rats. Pak J Pharm Sci 23: 266-72.
Bano S1, Sherkheli MA., 2003 Inhibition of tryptophan - pyrrolase activity and elevation of brain tryptophan concentration by fluoxetine in rats J Coll Physicians Surg Pak. 13(1):5-10.
Bano, S., Oretti, R. G., Morgan, C. J., Badawy, A. A.-B.,Buckland, P. R. and McGuffin, P., 1996. Effects of chronic administration and subsequent withdrawal of ethanol-containing liquid diet on rat liver tryptophan pyrrolase and tryptophan metabolism. Alcohol and Alcoholism 31: 205-215.
Calabozo B, Molina V, and Uribe F., 2016. Tianeptine: Why has it not been classified as a narcotic in Spain? Rev Psiquiatr Salud Ment (Barc.). 9:176---177.
Cutler MG, Rodgers RJ, Jackson JE., 1997. Behavioural effects in mice of subchronic buspirone, ondansetron and tianeptine. I. Social interactions. Pharmacol Biochem Behav. 56(2):287-93
Ding ZM, Oster SM, Hauser SR, Toalston JE, Bell RL, et al., 2012. Synergistic self-administration of ethanol and cocaine directly into the posterior ventral tegmental area: involvement of serotonin-3 receptors. J Pharmacol Exp Ther 340: 202-209.
Fattaccini, C.M., Bolanos-Jimenez, F., Gozlan, H. and Hamon M., 1990.Tianeptine stimulates uptake of 5-hydroxytryptamine in vivo in the rat brain. Neuropharmacology 29: 1-8.
Favre JD1, Guelfi-Sozzi C, Delalleau B, Lôo H. 1997., Tianeptine and alcohol dependence. Eur Neuropsychopharmacol. 3:S347-51.
Fernstrom JD., 1983. Role of precursor availability in control of monoamine biosynthesis in brain. Physiol Rev 63, 484–546.
File SE, Andrews N, al_ Farhan M., 1993. Anxiogenic responses of rats on withdrwal from chronic ethanol treatment effects of tianeptine. Alcohol Alcohol 28 (3): 281-6
Flügge G., 1999. Effects of cortisol on brain alpha2-adrenoceptors: potential role in stress. 1999 Neurosci Biobehav Rev.23(7):949-56.
Fuchs E, Flügge G., 2003. Chronic social stress: effects on limbic brain structures. Physiol Behav 79, 417-27
Garbutt JC, West SL, Carey TS, Lohr KN, Crews FT., Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA. 1999; 281:1318–25.
Harper C, Matsumoto I, Pfefferbaum A, Adalsteinsson E, Sullivan E V, Lewohl J, Dodd P, Taylor M, Fein G, and Landman B., 2005.The Pathophysiology of ‘Brain Shrinkage’ in Alcoholics – Structural and Molecular Changes and Clinical Implications. Alcohol Clin Exp Res, 29 (6): 1106–1115
Heinz A, Jones DW, Mazzanti C, Goldman D, Ragan P, Hommer D, Linnoila M, W;einberger DR., 2000. Serotonin transporter genotype interacts with in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry 47:643– 649.
Henry JL, Yashpal K., 1984. Rat brain slicer. A simple device for rapidly obtaining serial slabs of fresh brain. Brain Res Bull 13(1):195-7.
Hindmarch I(1)., 2001 Expanding the horizons of depression: beyond the monoamine hypothesis. Hum Psychopharmacol. 16(3):203-218
Hunter BE, Riley JN, Walker DW., 1975. Ethanol dependence in the rat: a parametric analysis Pharmacol Biochem Behav 3 (4): 619-29.
Hwang SM1, Lim SH1, Oh DJ1, Kim SK2, Jung HH1, Im GJ1., 2016. Effects of Tianeptine on Depressed Tinnitus Patients. J Audiol Otol. 20(2):90-6.
Jang MH1, Shin MC, Lee TH, Kim YP, Jung SB, Shin DH, Kim H, Kim SS, Kam EH., 2002.Alcohol and nicotine administration inhibits serotonin synthesis and tryptophan hydroxylase expression in dorsal and median raphe of young rats.Neuroscie. Lett. 329(2):141-4.
Johnson BA., 2004. Role of the serotonergic system in the neurobiology of alcoholism: implications for treatment. CNS Drugs 18(15):1105-18.
Ketcherside A, Matthews I and Filbey F., 2013 The Serotonin Link between Alcohol Use and Affective Disorders Journal of addiction and prevention.1(2);1-5
Koob GF. 2000. Neurobiology of addiction..Toward the development of new therapies. Ann N Y Acad Sci 909:170-85.
Kranzler H, Lappalainen J, Nellissery M, Gelernter J., 2002. Association study of alcoholism subtypes with a functional promoter polymorphism in the serotonin transporter protein gene. Alcohol Clin Exp Res 26(9):1330-5.
Liu W1, Shu XJ2, Chen FY3, Zhu C3, Sun XH3, Liu LJ2, Ai YX2, Li YG4, Zhao H5.,Tianeptine reverses stress-induced asymmetrical hippocampal volume and N-acetylaspartate loss in rats: an in vivo study .Psychiatry Res 2011; 194 (3).385-392.
Majchrowicz E., 1975. Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 17, 43(3):245-54.
Malagié I, Deslandes A, Gardier AM., 2000. Effects of acute and chronic tianeptine administration on serotonin outflow in rats: comparison with paroxetine by using in vivo microdialysis. Eur J Pharmacol 403(1-2):55-65.
Malka, R., Loo,H., Ganry,H. et al., 1992. Long-term administration of tianeptine in depressed patients after alcohol withdrawal. British Journal of Psychiatry 160 (Suppl. 15), 66–71.
Mantere T, Tupala E, Hall H, Sarkioja T, Rasanen P, Bergstrom K, et al., Serotonin transporter distribution and density in the cerebral cortex of alcoholic and nonalcoholic comparison subjects: a whole-hemisphere autoradiography study. Am J Psychiatry. 2002; 159:599–606
Martijena ID, Bustos SG, Bertotto ME, Molina VA., 2005. Antidepressants attenuate both the enhanced ethanol intake and ethanol-induced anxiolytic effects in diazepam withdrawal rats. Eur Neuropsychopharmacol. Jan 15(1):119-30.
McEwen BS1, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E., 2010. The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation. Mol Psychiatry.15(3):237-49.
Mennini T, Garratini S., 1991. Neurobiology of Tianeptine. A new pharmaceutic agent Presse Med 20(37):1823-7.
Miller FT1, Freilicher J., 1995. Comparison of TCAs and SSRIs in the treatment of major depression in hospitalized geriatric patients. J Geriatr Psychiatry Neurol. .8(3):173-6. Miller NS1. 1995. Pharmacotherapy in alcoholism. J Addict Dis.14(1):23-46
Naranjo CA, Kadlec KE, Sanhueza P, Woodley-Remus D, Sellers EM.,1990. Fluoxetine differentially alters alcohol intake and otherConsummatory behaviors in problem drinkers. Clin Pharmacol Ther. 47(4):490–498.
Naranjo CA, Poulos CX, Bremner KE, Lanctot K L., 1994. Fluoxetine attenu¬ates alcohol intake and desire to drink. Int Clin Psychopharmacol.;9(3):163–172.
Naranjo CA1, Knoke DM, Bremner KE.., 2000. Variations in response to citalopram in men and women with alcohol dependence. J Psychiatry Neurosci. 25(3):269-75.
Naranjo CA1, Poulos CX, Bremner KE, Lanctôt KL., 1992. Citalopram decreases desirability, liking, and consumption of alcohol in alcohol-dependent drinkers Clin Pharmacol Ther.;51(6):729-39.
Oluyomi AO, Datla KP, Curzon G., 1997. Effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine on 5-HT Pinduced behaviour. Neuropharmacology 36: 383-7.
Oretti R, Bano S, Morgan CJ, Badawy AA, Bonner A, Buckland P, McGuffin P., 1996. Prevention by cyclohexamide of the audiogenic seizures and tryptophan metabolic disturbances of ethanol withdrawal in rats. Alcohol Alcohol 31(3): 243-7.
Oscar-Berman, M and Marinkvoic K., 2003. Alcoholism and the brain. Alcohol Research and health. 27(2): 125-33
Oscar-Berman, M., 2000. Neuropsychological vulnerabilities in chronic alcoholism. In: Noronha, A.; Eckardt, M.J.; and Warren, K.. Review of NIAAA’s Neuroscience and Behavioral Research Portfolio. 34:437–471.
Overstreet DH1, Knapp DJ, Breese GR., 2004 Similar anxiety-like responses in male and female rats exposed to repeated withdrawals from ethanol. Pharmacol Biochem Behav. 78(3):459-64.
Paxinos G and Watson C., 1982. The Rat brain in stereotaxic coordinates
Pihl, R. O and Le Marquand, D.1998. Serotonin and aggression and the alcohol-aggression Relationship. Alcohol & Alcoholism. 33(1):55-65
Richard DM1, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM.L., 2009. Tryptophan basic metabolic functions.Behavioural Research and Therapeutic indications Int J Tryptophan Res. 23;2:45-60.
Rodgers RJ(1), Cutler MG, Jackson JE., 1997. Behavioural effects in mice of subchronic buspirone, ondansetron and tianeptine. II. The elevated plus-maze Pharmacol Biochem Behav. 56(2):295-303.
Rosennloom, M.J., and Pfefferbaum, A., 2008.Magnetic resonance imaging of the living brain: Evidence for brain degeneration among alcoholics and recovery with abstinence. Alcohol Research and Health 31:362–376,
Sanchez C., 2006. The pharmacology of citalopram enantiomers: the antagonism by R-citalopram on the effect of S-citalopram. Basic Clin Pharmacol Toxicol. 99:91–5.
Sari Y, Johnson VR, Weedman JM., 2011. Role of the serotonergic system in Alcohol dependence: From animal models to Clinics. Prog Mol. Biol Transl Sci 98: 401–443.
Sarnyai Z1, Shaham Y, Heinrichs SC., 2001 The role of corticotropin-releasing factor in drug addiction. Pharmacol Rev. 53(2): 209-43.
Storvik M, Haukijarvi T, Tupala E, Tiihonen J., 2008. Correlation between the SERT binding densities in hypothalamus and amygdala in Cloninger type 1 and 2 alcoholics. Alcohol Alcohol. 43:25–30.
Thompson, W. L., 1978. Management of alcohol withdrawal syndromes. Advances in Internal Medicine 138: 278–283.
Uzbay IT., 2008 Serotonergic anti-depressants and ethanol withdrawal syndrome: a review. Alcohol Alcohol 43(1): 15-24
Uzbay, I. T. and Kayaalp, S. O., 1995. A modified liquid diet of chronic ethanol administration: Validation by ethanol withdrawal syndrome in rats. Pharmacological Research 31: 37–42.
Uzbekov MG., 2009 Antidepressant action of tianeptine is connected with acceleration of serotonin turnover in the synapse: a hypothesis. Neuropsychopharmacol Hung. 11(2):83-7.
Uzbay IT (1), Kayaalp SO., 1995. A modified liquid diet of chronic ethanol administration: validation by ethanol withdrawal syndrome in rats. Pharmacol Res. 31(1):37-42.
Vadachkoria D1, Gabunia L, Gambashidze K, Pkhaladze N, Kuridze., .2009. N Addictive potential of Tianeptine - the threatening reality. Georgian Med News. 174:92-4.
Virkkunen M, Kallio E, Rawlings R, Tokola R, Poland RE, Guidotti A, Nemeroff C, Bissette G , Kalogeras K, Karonen SL et al., 1994. Personality profile and state aggressiveness in Finnish alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatr. 51(1): 28-33.
Warner-Schmidt JL, Duman RS., 2006. Hippocampal neurogenesis: Opposing effects of stress and antidepressant treatment. Hippocampus 16 (3): 239-49.
Whitton PS, Sarna GS, Datla KP, Curzon G., 1991. Effects of tianeptine on stress-induced behavioural deficits and 5-Ht dependent behavior. Psychopharmacology (Berl). 104 (1):81-5.
Zahr NM1, Pfefferbaum A1. .,2017. Alcohol’s effects on the brain: Neuroimaging results in human and animal models. Alcohol Res. 38(2):183-206.
Zhong H, Hansen KB, Boyle NJ, Han K, Muske G, Huang X, Egebjerg J, Sanchez C., 2009. An allosteric binding site at the human serotonin transporter mediates the inhibition of escitalopram by R-citalopram: kinetic binding studies with the ALI/VFL-SI/TT mutant. Neurosci Lett.
Zhou L1, Huang KX, Kecojevic A, Welsh AM, Koliatsos VE., 2006. Evidence that serotonin reuptake modulators increase the density of serotonin innervation in the forebrain. J Neurochem. 96. (2):396-406. Epub 2005
- There are currently no refbacks.
Copyright (c) 2019 Indonesian Journal of Pharmacy
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Indonesian J Pharm indexed by:View My Stats