Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors

In Vitro and In Vivo Studies

Grzegorz Satała, Beata Duszyńska, Katarzyna Stachowicz, Anna Rafalo, Bartlomiej Pochwat, Christine Luckhart, Paul R. Albert, Mireille Daigle, Kenji Tanaka, René Hen, Tomasz Lenda, Gabriel Nowak, Andrzej J. Bojarski, Bernadeta Szewczyk

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Recent data has indicated that Zn can modulate serotonergic function through the 5-HT1A receptor (5-HT1AR); however, the exact mechanisms are unknown. In the present studies, radioligand binding assays and behavioural approaches were used to characterize the pharmacological profile of Zn at 5-HT1ARs in more detail. The influence of Zn on agonist binding to 5-HT1ARs stably expressed in HEK293 cells was investigated by in vitro radioligand binding methods using the agonist [3H]-8-OH-DPAT. The in vivo effects of Zn were compared with those of 8-OH-DPAT in hypothermia, lower lip retraction (LLR), 5-HT behavioural syndrome and the forced swim (FST) tests. In the in vitro studies, biphasic effects, which involved allosteric potentiation of agonist binding at sub-micromolar Zn concentrations and inhibition at sub-millimolar Zn concentrations, were found. The in vivo studies showed that Zn did not induce LLR or elements of 5-HT behavioural syndrome but blocked such effects induced by 8-OH-DPAT. Zn decreased body temperature in rats and mice; however, Zn failed to induce hypothermia in the 5-HT1A autoreceptor knockout mice. In the FST, Zn potentiated the effect of 8-OH-DPAT. However, in the FST performed with the 5-HT1A autoreceptor knockout mice, the anti-immobility effect of Zn was partially blocked. Both the binding and behavioural studies suggest a concentration-dependent dual mechanism of Zn action at 5-HT1ARs, with potentiation at low dose and inhibition at high dose. Moreover, the in vivo studies indicate that Zn can modulate both presynaptic and postsynaptic 5-HT1ARs; however, Zn’s effects at presynaptic receptors seem to be more potent.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalMolecular Neurobiology
DOIs
Publication statusAccepted/In press - 2015 Dec 12

Fingerprint

8-Hydroxy-2-(di-n-propylamino)tetralin
Receptor, Serotonin, 5-HT1A
Autoreceptors
Lip
Hypothermia
Knockout Mice
Serotonin
Presynaptic Receptors
Radioligand Assay
HEK293 Cells
Body Temperature
Pharmacology
In Vitro Techniques
hydroxide ion

Keywords

  • 5-HT
  • Autoreceptor
  • Behavioural studies
  • Binding
  • Depression
  • Serotonin
  • Zn

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Satała, G., Duszyńska, B., Stachowicz, K., Rafalo, A., Pochwat, B., Luckhart, C., ... Szewczyk, B. (Accepted/In press). Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies. Molecular Neurobiology, 1-13. https://doi.org/10.1007/s12035-015-9586-3

Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors : In Vitro and In Vivo Studies. / Satała, Grzegorz; Duszyńska, Beata; Stachowicz, Katarzyna; Rafalo, Anna; Pochwat, Bartlomiej; Luckhart, Christine; Albert, Paul R.; Daigle, Mireille; Tanaka, Kenji; Hen, René; Lenda, Tomasz; Nowak, Gabriel; Bojarski, Andrzej J.; Szewczyk, Bernadeta.

In: Molecular Neurobiology, 12.12.2015, p. 1-13.

Research output: Contribution to journalArticle

Satała, G, Duszyńska, B, Stachowicz, K, Rafalo, A, Pochwat, B, Luckhart, C, Albert, PR, Daigle, M, Tanaka, K, Hen, R, Lenda, T, Nowak, G, Bojarski, AJ & Szewczyk, B 2015, 'Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies', Molecular Neurobiology, pp. 1-13. https://doi.org/10.1007/s12035-015-9586-3
Satała, Grzegorz ; Duszyńska, Beata ; Stachowicz, Katarzyna ; Rafalo, Anna ; Pochwat, Bartlomiej ; Luckhart, Christine ; Albert, Paul R. ; Daigle, Mireille ; Tanaka, Kenji ; Hen, René ; Lenda, Tomasz ; Nowak, Gabriel ; Bojarski, Andrzej J. ; Szewczyk, Bernadeta. / Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors : In Vitro and In Vivo Studies. In: Molecular Neurobiology. 2015 ; pp. 1-13.
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