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Repeated amphetamine administration in rats revealed consistency across days and a complete dissociation between locomotor and hypothalamic-pituitary-adrenal axis effects of the drug

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Abstract

Rationale

Most drugs of abuse stimulate both locomotor activity and the hypothalamic-pituitary-adrenal (HPA) axis, but the relationship between the two responses within the same subjects and their reliabilities has been scarcely studied. Our objectives were to study: (1) the consistency and stability across time of locomotor and HPA activation induced by repeated d-amphetamine (AMPH); (2) the relationship between locomotor and hormonal responses to AMPH; and (3) the relationship between novelty-induced activity and both types of responses to the drug.

Methods

Male adult rats were exposed to a novel environment to study the locomotor response. Later, they were injected with AMPH (2 mg/kg, sc) for 5 days. In Experiment 1, Plasma adrenocorticotropin (ACTH) and corticosterone levels in response to AMPH were studied on days 1, 3, and 5, and locomotor response on days 2 and 4. In Experiment 2, ACTH and corticosterone responses were studied on days 2 and 4, and locomotor response on days 1, 3, and 5.

Results

Across days, both locomotor and HPA responses to the drug were consistent, but independent measures, unrelated to the reactivity to novelty. As measured by the area under the curve, the HPA response to AMPH desensitized with the repeated injection, whereas the initial locomotor response to the drug increased.

Conclusions

Dissociation exists between HPA and locomotor activation induced by AMPH, which seemed to be both reliable individual traits. Locomotor reactivity to novelty was related neither to HPA nor to locomotor responses to AMPH.

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Acknowledgements

We thank the following Institutions from Spain for funding this research: Ministerio de Ciencia e Innovación (SAF2008-01175), Instituto de Salud Carlos III (Redes temáticas de Investigación Cooperativa en Salud, RD06/0001/0015), Ministerio de Sanidad y Consumo (Plan Nacional sobre Drogas) and Generalitat de Catalunya (SGR2009-16).

Animal Care

This research has been conducted according to the “Principles of laboratory animal care” and was carried out in accordance with the European Communities Council Directive (86/609/EEC).

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Authors and Affiliations

  1. Institute of Neurosciences, Autonomous University of Barcelona, Bellaterra, Barcelona, 08193, Spain

    Humberto Gagliano, Raül Andero, Antonio Armario & Roser Nadal

  2. Animal Physiology (School of Biosciences), Autonomous University of Barcelona, Bellaterra, Barcelona, 08193, Spain

    Humberto Gagliano, Raül Andero & Antonio Armario

  3. Psychobiology (School of Psychology), Bellaterra, Barcelona, 08193, Spain

    Roser Nadal

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  1. Humberto Gagliano
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  2. Raül Andero
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  3. Antonio Armario
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  4. Roser Nadal
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Correspondence to Roser Nadal.

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Gagliano, H., Andero, R., Armario, A. et al. Repeated amphetamine administration in rats revealed consistency across days and a complete dissociation between locomotor and hypothalamic-pituitary-adrenal axis effects of the drug. Psychopharmacology 207, 447–459 (2009). https://doi.org/10.1007/s00213-009-1676-3

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