Skip to main content
SpringerLink
Log in

Increased antidepressant-like effect of desipramine combined with central stimulants (caffeine and amphetamine) in mice

  • Research Article
  • Published:
Central European Journal of Biology

Abstract

Desipramine is a widely used antidepressive agent that inhibits the reuptake of noradrenaline and serotonin, and central stimulants such as caffeine and amphetamine help to release noradrenaline and serotonin. This work aimed to evaluate whether the combination of these agents could produce a stronger antidepressant-like effect than either of the drugs alone. To this end, male mice were treated with different doses of desipramine, caffeine, amphetamine, desipramine-caffeine and desipramine-amphetamine. The results showed that all drugs produced decreased immobility time in the forced swimming model. The combined treatment of desipramine (0.31, 1.0 or 3.1 mg/kg i.p.) with caffeine or amphetamine (0.31 or 1 mg/kg i.p.) reduced immobility time greater than either of those drugs alone. The combined treatment of desipramine (0.31, 1 and 3.1 mg/kg i.p.) with amphetamine or caffeine (0.1 and 1 mg/kg i.p.) did not increase the motor activity significantly compared to the control. These results also suggested that drugs which promote the release of noradrenaline and serotonin could increase antidepressant-like effect of desipramine.

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

  1. López J.J., Diagnostic and Statistical Manual of Mental Disorders (DSM IV) [Manual diagnóstico y estadístico de los trastornos mentales.], Masson Press, Spain, 2001 (in Spanish)

    Google Scholar 

  2. Heinze G., Depression: a visual phenomenon [La depresión un fenómeno visual], Med Int Mex, 2001, 16, 308–326 (in Spanish)

    Google Scholar 

  3. Garlow S.J., Musselman D.L., Nemeroff C.B., The neurochemistry of mood disorders: clinical studies, In: Charney D.S., Nestler E.J., (Eds.), Neurobiology of Mental Illness, Oxford University Press, New York, 1999

    Google Scholar 

  4. Schildkraut J.J., The catecholamine hypothesis of affective disorders: a review of supporting evidence, Am J Psychiatry, 1965, 122, 509–522

    PubMed  CAS  Google Scholar 

  5. Maas J.W., Fawcett J.A., Dekirmenjian H., Catecholamine metabolism, depressive illness, and drug response, Arch Gen Psychiatry, 1972, 26, 252–262

    Article  PubMed  CAS  Google Scholar 

  6. Schildkraut J.J., Norepinephrine metabolites as biochemical criteria for classifying depressive disorders and predicting responses to treatment: preliminary findings, Am J Psychiatry, 1973, 130, 695–699

    PubMed  CAS  Google Scholar 

  7. Maes M., Jacobs M.P., Suy E., Minner B., Leclercq C., Christiaens F., et al., Suppressant effects of dexamethasone on the availability of plasma L-tryptophan and tyrosine in healthy controls and in depressed patients, Acta Psychiatr Scand, 1990, 81, 19–23

    Article  PubMed  CAS  Google Scholar 

  8. Gibbons R.D., Davis J.M., Consistent evidence for a biological subtype of depression characterized by low CSF monoamine levels, Acta Psychiatr Scand, 1986, 74, 8–12

    Article  PubMed  CAS  Google Scholar 

  9. Van Praag H.M., Depression, suicide and the metabolism of serotonin in the brain, J Affect Disord, 1982, 4, 275–290

    Article  PubMed  Google Scholar 

  10. Nyback H.V., Walters J.R., Aghajanian G.K., Roth R.H., Tricyclic antidepressants: effects on the firing rate of brain noradrenergic neurons, Eur J Pharmacol, 1975, 32, 302–312

    Article  PubMed  CAS  Google Scholar 

  11. Sonsalla P.K., The role of N-methyl-D-aspartate receptors in dopaminergic neuropathology produced by the amphetamines, Drug Alcohol Depend, 1995, 37, 101–105

    Article  PubMed  CAS  Google Scholar 

  12. Orr K., Taylor D., Psychostimulants in the treatment of depression: a review of the evidence, CNS Drugs, 2007, 21, 239–257

    Article  PubMed  CAS  Google Scholar 

  13. Borsini F., Meli A., Is the forced swimming test a suitable model for revealing antidepressant activity?, Psychopharmacology (Berl), 1988

  14. Porsolt R.D., Bertin A., Blavet N., Deniel M., Jalfre M., Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity, Eur J Pharmacol, 1979, 57, 201–210

    Article  PubMed  CAS  Google Scholar 

  15. Cruz S.L., Soberanes-Chavez P., Paez-Martinez N., Lopez-Rubalcava C., Toluene has antidepressant-like actions in two animal models used for the screening of antidepressant drugs, Psychopharmacology (Berl), 2009, 204, 279–286

    Article  CAS  Google Scholar 

  16. Tallarida R.J., Drug Synergism and Dose-Effect Data Analysis, Taylor & Francis, Inc., Boca Raton, 2000

    Book  Google Scholar 

  17. Vieira C., De Lima T.C., Carobrez Ade P., Linode-Oliveira C., Frequency of climbing behavior as a predictor of altered motor activity in rat forced swimming test, Neurosci Lett, 2008, 445, 170–173

    Article  PubMed  CAS  Google Scholar 

  18. Enriquez-Castillo A., Alamilla J., Barral J., Gourbiere S., Flores-Serrano A.G., Gongora-Alfaro J.L., et al., Differential effects of caffeine on the antidepressant-like effect of amitriptyline in female rat subpopulations with low and high immobility in the forced swimming test, Physiol Behav, 2008, 94, 501–509

    Article  PubMed  CAS  Google Scholar 

  19. Mossner R., Albert D., Persico A.M., Hennig T., Bengel D., Holtmann B., et al., Differential regulation of adenosine A(1) and A(2A) receptors in serotonin transporter and monoamine oxidase A-deficient mice, Eur Neuropsychopharmacol, 2000, 10, 489–493

    Article  PubMed  CAS  Google Scholar 

  20. Regenold J.T., Illes P., Inhibitory adenosine A1-receptors on rat locus coeruleus neurones. An intracellular electrophysiological study, Naunyn Schmiedebergs Arch Pharmacol, 1990, 341, 225–231

    Article  PubMed  CAS  Google Scholar 

  21. Okada M., Zhu G., Yoshida S., Iwasa H., Kaneko S., Mechanisms of interaction between adenosine receptor subtypes on hippocampal serotonin release, Jap. J. Psychopharmacol., 2002, 22, 61–69 (in Japanese)

    CAS  Google Scholar 

  22. Shaheen A.A., Hamdy M.A., Kheir-Eldin A.A., Lindstrom P., el-Fattah A.A., Effect of pretreatment with vitamin E or diazepam on brain metabolism of stressed rats, Biochem Pharmacol, 1993, 46, 194–197

    Article  PubMed  CAS  Google Scholar 

  23. Kulkarni S.K., Mehta A.K., Purine nucleoside—mediated immobility in mice: reversal by antidepressants, Psychopharmacology (Berl), 1985, 85, 460–463

    Article  CAS  Google Scholar 

  24. Zhang H.T., Whisler L.R., Huang Y., Xiang Y., O’Donnell J.M., Postsynaptic alpha-2 adrenergic receptors are critical for the antidepressantlike effects of desipramine on behavior, Neuropsychopharmacology, 2009, 34, 1067–1077

    Article  PubMed  CAS  Google Scholar 

  25. Rogoz Z., Potentiation of the antidepressant-like effect of desipramine or reboxetine by metyrapone in the forced swimming test in rats, Pharmacol Rep, 2009, 61, 1173–1178

    PubMed  CAS  Google Scholar 

  26. Fredholm B.B., Battig K., Holmen J., Nehlig A., Zvartau E.E., Actions of caffeine in the brain with special reference to factors that contribute to its widespread use, Pharmacol Rev, 1999, 51, 83–133

    PubMed  CAS  Google Scholar 

  27. Schlosberg A.J., Acute and chronic effects of caffeine on brain monoamine levels and endocrine function in the rat, Arch Int Pharmacodyn Ther, 1984, 267, 149–160

    PubMed  CAS  Google Scholar 

  28. Robertson D., Frolich J.C., Carr R.K., Watson J.T., Hollifield J.W., Shand D.G., et al., Effects of caffeine on plasma renin activity, catecholamines and blood pressure, N Engl J Med, 1978, 298, 181–186

    Article  PubMed  CAS  Google Scholar 

  29. Lorden J.F., Nunn W.B., Effects of central and peripheral pretreatment with fluoxetine in gustatory conditioning, Pharmacol Biochem Behav, 1982, 17, 435–443

    Article  PubMed  CAS  Google Scholar 

  30. Daniel WA, Kot M., Wojcikowski J., Effects of classic and newer antidepressants on the oxidation pathways of caffeine in rat liver. In vitro study, Pol J Pharmacol, 2003, 55, 1045–1053

    PubMed  CAS  Google Scholar 

  31. Bourin M., Colombel M.C., Malinge M., Bradwejn J., Clonidine as a sensitizing agent in the forced swimming test for revealing antidepressant activity, J Psychiatry Neurosci, 1991, 16, 199–203

    PubMed  CAS  Google Scholar 

  32. Kalisker A., Waymire J.C., Rutledge C.O., Effects of 6-hydroxydopamine and reserpine on amphetamine-induced release of norepinephrine in rat cerebral cortex, J Pharmacol Exp Ther, 1975, 193, 64–72

    PubMed  CAS  Google Scholar 

  33. Lewander T., Effects of amphetamine on urinary and tissue catecholamines in rats after inhibition of its metabolism with desmethylimipramine, Eur J Pharmacol, 1968, 5, 1–9

    Article  PubMed  CAS  Google Scholar 

  34. Dolfini E., Tansella M., Valzelli L., Garattini S., Further studies on the interaction between desipramine and amphetamine, Eur J Pharmacol, 1969, 5, 185–190

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Cinvestav, 07360, Mexico City, Mexico

    Evelyn Robles-Molina

  2. Chemistry Faculty, UAEmex, 50000, Toluca City, Mexico

    Daniel Millán

  3. Department of Pharmacobiology, Cinvestav, 14330, Mexico City, Mexico

    Enrique Hong

  4. Department of Pharmacology and Toxicology, Hospital Infantil de México Federico Gomez, 06720, Mexico City, Mexico

    Fengyang Huang

  5. Superior School of Medicine, National Polytechnic Institute, 11340, Mexico City, Mexico

    Santiago Villafaña

Authors
  1. Evelyn Robles-Molina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Millán
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Enrique Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fengyang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Santiago Villafaña
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Santiago Villafaña.

About this article

Cite this article

Robles-Molina, E., Millán, D., Hong, E. et al. Increased antidepressant-like effect of desipramine combined with central stimulants (caffeine and amphetamine) in mice. cent.eur.j.biol. 7, 391–396 (2012). https://doi.org/10.2478/s11535-012-0028-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11535-012-0028-1

Keywords

Search

Navigation