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

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Abstract

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.

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Acknowledgments

The authors thank “Farmapol” and “Cortex Pharmaceuticals” (Dr. Mark Varney) for the generous gift of compounds. This study was partially supported by Funds for Statutory Activity of the Institute of Pharmacology, Polish Academy of Sciences; Collegium Medicum, Jagiellonian University, Kraków and Medical University of Lublin.

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Authors and Affiliations

  1. Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland

    B. Szewczyk, M. Sowa-Kućma, K. Gołembiowska, A. Pilc & Gabriel Nowak

  2. Chair of Pharmacobiology, Collegium Medicum, Jagiellonian University, Medyczna 9, 30-688, Kraków, Poland

    A. Cichy, A. Siwek, M. Dybała & Gabriel Nowak

  3. Faculty of Health Sciences, Collegium Medicum, Jagiellonian University, Michałowskiego 20, 31-126, Kraków, Poland

    A. Pilc

  4. Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Staszica 4, 20-081, Lublin, Poland

    E. Poleszak & J. Listos

  5. Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland

    A. Wróbel

  6. Department of Rehabilitation and Physiology, Medical University of Lublin, Chodźki 6, 20-950, Lublin, Poland

    S. Słotwiński

  7. Department of Animal Physiology, Institute of Biology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland

    P. Wlaź

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Szewczyk, B., Poleszak, E., Sowa-Kućma, M. et al. The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in the forced swim test. Amino Acids 39, 205–217 (2010). https://doi.org/10.1007/s00726-009-0412-y

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