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The selective 5-HT1A receptor agonist NLX-112 displays anxiolytic-like activity in mice

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Abstract

Anxiety is amongst the commonest neuropsychiatric disorders, and there is a large body of evidence to suggest that abnormalities in serotonergic function are involved in its pathogenesis. Several studies have implicated 5-HT1A receptor activation in mitigating anxiety disorders, so this study investigated the acute effects of a highly selective, potent and efficacious 5-HT1A receptor full agonist, NLX-112 (a.k.a. befiradol, F13640), in middle-aged C57bl/6 J male mice. Video tracking was used to measure several parameters including time spent in the open and closed arms of an elevated plus maze (EPM), distance travelled and thigmotaxis in an open field test (OFT). At 0.1 to 1.0 mg/kg s.c., NLX-112 markedly decreased thigmotaxis and increased exploratory behaviour in the OFT and EPM assays. Hence, at 0.3 mg/kg, NLX-112 augmented locomotor activity in the centre of an open field arena by 164% and increased the time spent in the open arms of the EPM by 119% of control. These results indicate that anxiety-like behaviours in mice are significantly diminished with low doses of NLX-112. NLX-112 may therefore possess anxiolytic properties which complement its known activity in models of movement disorders.

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All raw data and graphs are available on request. All data were generated in-house, and no “paper mill” was used.

Abbreviations

AIMS:

Abnormal involuntary movements

EPM:

Elevated plus maze

LID:

Levodopa-induced dyskinesia

OFT:

Open field test

PET:

Positron emission tomography

PD:

Parkinson’s disease

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Funding

This work was supported through the collaborative venture of the Hertfordshire Science Partnership, Neurolixis and the European Regional Development Fund.

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Authors and Affiliations

  1. Department of Clinical Pharmaceutical and Biological Science, University of Hertfordshire, Hatfield, UK

    William H. Powell & Mahmoud M. Iravani

  2. Department of Psychology, School of Life and Medical Sciences, College Lane, University of Hertfordshire, Hatfield, AL10 9AB, UK

    Lucy E. Annett

  3. Neurolixis SAS, 2 Rue Georges Charpak, 81100, Castres, France

    Ronan Depoortere & Adrian Newman-Tancredi

Authors
  1. William H. Powell
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  2. Lucy E. Annett
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  3. Ronan Depoortere
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  4. Adrian Newman-Tancredi
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  5. Mahmoud M. Iravani
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Contributions

The contribution of co-authors were as follows: WHP, in vivo investigation, data collection and curation, preparation of figures, writing original draft and data analysis; LEA, editing, reviewing and provision of equipment; RD, editing, reviewing and statistical analysis oversight and data interpretation; AN-T, supervision, data interpretation, editing and reviewing; MMI, in vivo experimental design, supervision; manuscript revisions, and reviewing data validation. We declare that all authors read and approved the manuscript.

Corresponding author

Correspondence to Mahmoud M. Iravani.

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Ethics approval

The studies undertaken here were approved under knowledge and approval of local Animal Welfare Ethical Review Body and were carried out in accordance with the UK Animals (Scientific Procedures) Act 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments.

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Not applicable. No human participants took part in this study.

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We have the consent of all co-authors and the institution to publish this research article.

Competing interests

A. Newman-Tancredi and R. Depoortere are employees and shareholders of Neurolixis. The other authors declare no competing interest in respect to the research, authorship and publication of this research article.

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Powell, W.H., Annett, L.E., Depoortere, R. et al. The selective 5-HT1A receptor agonist NLX-112 displays anxiolytic-like activity in mice. Naunyn-Schmiedeberg's Arch Pharmacol 395, 149–157 (2022). https://doi.org/10.1007/s00210-021-02183-2

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