Amino Acids

, Volume 39, Issue 1, pp 205–217 | Cite as

The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in the forced swim test

  • B. Szewczyk
  • E. Poleszak
  • M. Sowa-Kućma
  • A. Wróbel
  • S. Słotwiński
  • J. Listos
  • P. Wlaź
  • A. Cichy
  • A. Siwek
  • M. Dybała
  • K. Gołembiowska
  • A. Pilc
  • Gabriel Nowak
Original Article


Antidepressant-like activity of zinc in the forced swim test (FST) was demonstrated previously. Enhancement of such activity by joint administration of zinc and antidepressants was also shown. However, mechanisms involved in this activity have not yet been established. The present study examined the involvement of the NMDA and AMPA receptors in zinc activity in the FST in mice and rats. Additionally, the influence of zinc on both glutamate and aspartate release in the rat brain was also determined. Zinc-induced antidepressant-like activity in the FST in both mice and rats was antagonized by N-methyl-d-aspartic acid (NMDA, 75 mg/kg, i.p.) administration. Moreover, low and ineffective doses of NMDA antagonists (CGP 37849, L-701,324, d-cycloserine, and MK-801) administered together with ineffective doses of zinc exhibit a significant reduction of immobility time in the FST. Additionally, we have demonstrated the reduction of immobility time by AMPA receptor potentiator, CX 614. The antidepressant-like activity of both CX 614 and zinc in the FST was abolished by NBQX (an antagonist of AMPA receptor, 10 mg/kg, i.p.), while the combined treatment of sub-effective doses of zinc and CX 614 significantly reduces the immobility time in the FST. The present study also demonstrated that zinc administration potentiated a veratridine-evoked glutamate and aspartate release in the rat’s prefrontal cortex and hippocampus. The present study further suggests the antidepressant properties of zinc and indicates the involvement of the NMDA and AMPA glutamatergic receptors in this activity.


Forced swim test Antidepressant Zinc NMDA AMPA Glutamate receptors 


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • B. Szewczyk
    • 1
  • E. Poleszak
    • 4
  • M. Sowa-Kućma
    • 1
  • A. Wróbel
    • 5
  • S. Słotwiński
    • 6
  • J. Listos
    • 4
  • P. Wlaź
    • 7
  • A. Cichy
    • 2
  • A. Siwek
    • 2
  • M. Dybała
    • 2
  • K. Gołembiowska
    • 1
  • A. Pilc
    • 1
    • 3
  • Gabriel Nowak
    • 1
    • 2
  1. 1.Institute of PharmacologyPolish Academy of SciencesKrakówPoland
  2. 2.Chair of Pharmacobiology, Collegium MedicumJagiellonian UniversityKrakówPoland
  3. 3.Faculty of Health Sciences, Collegium MedicumJagiellonian UniversityKrakówPoland
  4. 4.Department of Pharmacology and PharmacodynamicsMedical University of LublinLublinPoland
  5. 5.Second Department of GynecologyMedical University of LublinLublinPoland
  6. 6.Department of Rehabilitation and PhysiologyMedical University of LublinLublinPoland
  7. 7.Department of Animal Physiology, Institute of BiologyMaria Curie-Skłodowska UniversityLublinPoland

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