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Kynurenic acid and alcohol and cocaine dependence: novel effects and multiple mechanisms?

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Abbreviations

3-HAA:

3-Hydroxyanthranilic acid

3-HK:

3-Hydroxykynurenine

KA:

Kynurenic acid

K:

Kynurenine

KAT:

Kynurenine aminotransferase

KMO:

Kynurenine mono-oxygenase (kynurenine hydroxylase)

QA:

Quinolinic acid

Trp:

L-Tryptophan

TDO:

Tryptophan 2,3-dioxygenase

References

  • Badawy AA-B, Bano S (2016) Elevation of kynurenine metabolites in rat liver and serum: a potential additional mechanism of the alcohol aversive and anti-cancer effects of disulfiram? Alcohol Alcohol 51:20–26

    Article  PubMed  Google Scholar 

  • Badawy AA-B, Bano S, Steptoe A (2011) Tryptophan in alcoholism treatment I: kynurenine metabolites inhibit the rat liver mitochondrial low km aldehyde dehydrogenase activity, elevate blood acetaldehyde concentration and induce aversion to alcohol. Alcohol Alcohol 46:651–660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Badawy AA-B, Dougherty DM (2016) Assessment of the human kynurenine pathway: comparisons and clinical implications of ethnic and gender differences in plasma tryptophan, kynurenine metabolites and enzyme expressions at baseline and after acute tryptophan loading and depletion. Int J Tryptophan Res 9:31–49

    Article  PubMed  PubMed Central  Google Scholar 

  • Badawy AA-B, Morgan CJ (2007) Tryptophan metabolites as potent inhibitors of aldehyde dehydrogenase activity and potential alcoholism-aversion therapeutic agents. Int Cong Series 1304:344–351

    Article  CAS  Google Scholar 

  • Carpenedo R, Chiarugi A, Russi P, Lombardi G, Carla V, Pellicciari R, Mattoli L, Moroni F (1994) Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anticonvulsant activities. Neuroscience 61:237–244

    Article  CAS  PubMed  Google Scholar 

  • Chiarugi A, Carpenedo R, Molina MT, Mattoli L, Pellicciari R, Moroni F (1995) Comparison of the neurochemical and behavioral effects resulting from the inhibition of kynurenine hydroxylase and kynureninase. J Neurochem 65:1176–1183

    Article  CAS  PubMed  Google Scholar 

  • Clark CJ, Mackay GM, Smythe GA, Bustamante S, Stone TW, Phillips RS (2005) Prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition. Infect Immunity 73:5249–5251

    Article  CAS  Google Scholar 

  • Garver E, Ross AD, Tu G-C, Cao QN, Zhou F, Israel Y (2000) Paradigm to test drug-induced aversion to ethanol. Alcohol Alcohol 35:435–438

    Article  CAS  PubMed  Google Scholar 

  • Justinova Z, Mascia P, Wu H-Q, Secci ME, Redhi GH, Panlilio LV, Scherma M, Barnes C, Parashos A, Zara T, Fratta W, Solinas M, Pistis M, Bergman J, Kangas BD, Ferré S, Tanda G, Schwarcz R, Goldberg SR (2013) Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. Nature Neurosci 16:1652–1661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kita T, Morrison PF, Heyes MP, Markey SP (2002) Effects of systemic and central nervous system localized inflammation on the contributions of metabolic precursors to the L-kynurenine and quinolinic acid pools in brain. J Neurochem 82:258–268

    Article  CAS  PubMed  Google Scholar 

  • Murakami Y, Saito K (2013) Species and cell types difference in tryptophan metabolism. Int J Tryptophan Res 6(Suppl 1):47–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okuno A, Fukuwatari T, Shibata K (2011) High tryptophan diet reduced extracellular dopamine release via kynurenic acid production in rat striatum. J Neurochem 118:796–805

    Article  CAS  PubMed  Google Scholar 

  • Pawlak D, Tankiewicz A, Matys T, Buczko W (2003) Peripheral distribution of kynurenine metabolites and activity of kynurenine pathway enzymes in renal failure. J Physiol Pharmacol (Krakow) 54:175–189

    CAS  Google Scholar 

  • Röver S, Cesura A, Huguenin P, Ketter R, Szente A (1997) Synthesis and biochemical evaluation of N-(4phenylthiazol-2-yl) benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase. J Med Chem 40:4378–4385

    Article  PubMed  Google Scholar 

  • Saito K, Fujigaki S, Heyes MP, Shibata K, Takemura M, Fujii H, Wada H, Noma A, Seishima M (2000) Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiency. Am J Physiol Renal Physiol 279:F565–F572

    CAS  PubMed  Google Scholar 

  • Schroeder JP, Cooper DA, Schank JR, Lyle MA, Gaval-Cruz M, Ogbonmwan YE, Pozdeyev N, Freeman IPM, Edwards GL, Holmes PV, Weinshenker D (2010) Disulfiram attenuates drug-primed reinstatement of cocaine seeking via inhibition of dopamine b-hydroxylase. Neuropsychopharmacol 35:2440–2449

    Article  CAS  Google Scholar 

  • Stone W (1993) The neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev 45:309–385

    CAS  PubMed  Google Scholar 

  • Vengeliene V, Cannella N, Takahashi T, Spanagel R (2016) Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse. Psychopharmacol 233:3449–3459

    Article  CAS  Google Scholar 

  • Zwilling D, Huang S-Y, Sathyasaikumar KV, Notarangelo FM, Guidetti P, Wu H-Q, Lee J, Truong J, Andrews-Zwilling Y, Hsieh EW, Louie JY, Wu T, Scearce-Levie K, Patrick C, Adame A, Giorgini F, Moussaoui S, Laue G, Rassoulpour A, Flik G, Huang Y, Muchowski JM, Masliah E, Schwarcz R, Muchowski PJ (2011) Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell 145:863–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Abdulla A.-B. Badawy.

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Badawy, A.AB. Kynurenic acid and alcohol and cocaine dependence: novel effects and multiple mechanisms?. Psychopharmacology 234, 169–171 (2017). https://doi.org/10.1007/s00213-016-4486-4

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