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Psychostimulants and forced swim stress interaction: how activation of the hypothalamic-pituitary-adrenal axis and stress-induced hyperglycemia are affected

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Abstract

Rationale

We recently reported that simultaneous exposure to amphetamine and various stressors resulted in reduced hypothalamic-pituitary-adrenal (HPA) and glycemic responses to the stressors. Since this is a new and relevant phenomenon, we wanted to further explore this interaction.

Objectives

This study aims (i) to characterize the effect of various doses of amphetamine on the physiological response to a predominantly emotional stressor (forced swim) when the drug was given immediately before stress; (ii) to study if an interaction appears when the drug was given 30 min or 7 days before swim; and (iii) to know whether cocaine causes similar effects when given just before stress. Adult male rats were used and plasma levels of ACTH, corticosterone, and glucose were the outcomes.

Results

Amphetamine caused a dose-dependent activation of the HPA axis, but all doses reduced HPA and glycemic responses to swim when given just before the stressor. Importantly, during the post-swim period, the stressor potently inhibited the ACTH response to amphetamine, demonstrating mutual inhibition between the two stimuli. The highest dose of amphetamine also reduced the response to swim when given 30 min before stress, whereas it caused HPA sensitization when given 7 days before. Cocaine also reduced stress-induced HPA activation when given just before swim.

Conclusions

The present results demonstrate a negative synergy between psychostimulants (amphetamine and cocaine) and stress regarding HPA and glucose responses when rats were exposed simultaneously to both stimuli. The inhibitory effect of amphetamine is also observed when given shortly before stress, but not some days before.

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Acknowledgements

The laboratory was supported by Spanish grants to AA and/or RN from Plan Nacional sobre Drogas (2011/021), Ministerio de Economía y Competitividad (SAF2014-53876R), Instituto de Salud Carlos III (RD12/0028/0014, Redes Temáticas de Investigación Cooperativa en Salud, Ministerio de Sanidad y Consumo), and Generalitat de Catalunya (SGR2014-1020). RN is a recipient of an ICREA-ACADEMIA award (Generalitat de Catalunya). The funding sources had no role either in the design, collection, analysis, and interpretation of the data or in the decision to submit the article for publication. The UAB animal facility received funding from 2015FEDER7S-20IU16-001945.

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Authors and Affiliations

  1. Institut de Neurociències, CIBERSAM and Red de Transtornos Adictivos (RTA), Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain

    Humberto Gagliano, Juan Antonio Ortega-Sanchez, Roser Nadal & Antonio Armario

  2. Animal Physiology Unit (School of Biosciences), Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain

    Humberto Gagliano, Juan Antonio Ortega-Sanchez & Antonio Armario

  3. Psychobiology Unit (School of Psychology), Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain

    Roser Nadal

Authors
  1. Humberto Gagliano
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  2. Juan Antonio Ortega-Sanchez
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  3. Roser Nadal
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  4. Antonio Armario
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Contributions

AA and RN were responsible for the study concept and design, AA wrote the manuscript that was further discussed by all authors, HG was the main responsible for the experiment, data and statistical analysis, RN was responsible for statistical analysis supervision and JAO-S helped in the experiment. All authors have reviewed the manuscript and approved the final version submitted for publication.

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Correspondence to Antonio Armario.

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Electronic supplementary material

Supplementary Fig. 1

Time-course of the plasma ACTH response to 30 min of forced swim in animals that were or not given AMPH. The groups were as follows: veh-home (n = 8), receiving saline and returned to their home cages; veh-swim (n = 10), receiving saline and immediately exposed to forced swim (30 min); AMPH1-home, AMPH2-home, and AMPH4-home (n = 10 each), receiving either 1 or 2 or 4 mg/kg of d-AMPH and returned to their home cages; AMPH1-swim, AMPH2-swim, and AMPH4-swim (n = 10 each), receiving either 1 or 2 or 4 mg/kg of d-AMPH and immediately exposed to forced swim. IMMEDIATE indicates sampling immediately after forced swim, and R30 and R60 sampling at 30 or 60 min after the termination of swim exposure. For statistical details, see Fig. 1 (GIF 36 kb)

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Gagliano, H., Ortega-Sanchez, J.A., Nadal, R. et al. Psychostimulants and forced swim stress interaction: how activation of the hypothalamic-pituitary-adrenal axis and stress-induced hyperglycemia are affected. Psychopharmacology 234, 2859–2869 (2017). https://doi.org/10.1007/s00213-017-4675-9

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  • DOI: https://doi.org/10.1007/s00213-017-4675-9

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