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Sex-influence of nicotine and nitric oxide on motor coordination and anxiety-related neurophysiological responses

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Abstract

Rationale

Nitric oxide (NO) is a messenger synthesized in both the neuronal and glial populations by nitric oxide synthase type 1 (NOS1). Nicotine regulates NO production in a sex-dependent manner, both molecules being involved in motor function.

Objective

The present study evaluates sex differences in motor coordination, general movement, and anxiety-related responses resulting from both constant and continuous nicotine treatment and the genetic depletion of NOS1 activity.

Methods

Male and female mice were analyzed with the open-field and the rotarod tests. To understand the role of NO, knockout mice for NOS1 (NOS1−/−) were analyzed. Nicotine was administered continuously at a dose of 24 mg/kg/day via osmotic mini-pumps over 14 days because the behavioral effects elicited are similar to those observed with discontinuous administration.

Results

Data analyses revealed noteworthy sex differences derived from NOS1 depletion. Control NOS1−/− males exhibited an exacerbated anxiety-related response in relation to control NOS1−/− females and control wild-type (WT) males; these differences disappeared in the nicotine-administered NOS1−/− males. Additionally, nicotine administration differentially affected the horizontal movements of NOS1−/− females with respect to WT animals. NO depletion affected male but not female motor coordination improvement along the test days. However, the drug affected female motor coordination only at the end of the administration period.

Conclusions

We show for the first time that NO affects motor and anxiety behaviors in a sex-dependent manner. Moreover, the behavioral effects of constant nicotine administration are dimorphic and dependent on NO production.

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Acknowledgments

This work has been supported by the Ministerio de Ciencia y Tecnología (BFU2010-18284), the Ministerio de Sanidad, Política Social e Igualdad (Plan Nacional Sobre Drogas), and the Junta de Castilla y León (Centre for Regenerative Medicine and Cell Therapy of Castile and León).

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  1. Laboratory of Neural Plasticity and Neurorepair, Institute for Neuroscience of Castilla y León (INCyL), Universidad de Salamanca, C/ Pintor Fernando Gallego 1, 37007, Salamanca, Spain

    Rodrigo Muñoz-Castañeda, David Díaz, José R. Alonso & Eduardo Weruaga

  2. Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain

    Rodrigo Muñoz-Castañeda, David Díaz, Carmelo A. Ávila-Zarza, José R. Alonso & Eduardo Weruaga

  3. Department of Statistics, Universidad de Salamanca, Salamanca, Spain

    Carmelo A. Ávila-Zarza

  4. Institute for Higher Research, Universidad de Tarapacá, Arica, Chile

    José R. Alonso

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  1. Rodrigo Muñoz-Castañeda
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  2. David Díaz
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Correspondence to Eduardo Weruaga.

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Muñoz-Castañeda, R., Díaz, D., Ávila-Zarza, C.A. et al. Sex-influence of nicotine and nitric oxide on motor coordination and anxiety-related neurophysiological responses. Psychopharmacology 231, 695–706 (2014). https://doi.org/10.1007/s00213-013-3284-5

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