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Short-term fluoxetine treatment induces neuroendocrine and behavioral anxiogenic-like responses in adolescent male rats

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Abstract

Fluoxetine (FLX) is prescribed to treat depression and anxiety in adolescent patients. However, FLX has anxiogenic effects during the acute phase of treatment, and caution has been raised due to increased suicidal thinking and behavior. Herein, we sought to study in adolescent (35-day-old) male rats, the effects of short-term FLX treatment (10 mg/kg/day, i.p. for 3–4 days) on hypothalamic–pituitary–adrenal axis activity, serotonin (5-hidroxytriptamine, 5-HT) transporter (SERT) mRNA expression in the dorsal raphe nucleus (DRN), energy balance-related variables and behavioral profiles in the holeboard. Our results revealed that daily FLX administration increased plasma corticosterone (B) concentrations without affecting basal gene expression of corticotrophin releasing hormone in the hypothalamic paraventricular nucleus (PVN) nor of pro-opiomelanocortin in the anterior pituitary. However, FLX had significant effects increasing the mRNA expression of PVN arginine vasopressin (AVP) and reducing SERT mRNA levels in the dorsolateral subdivision of the DRN. In the holeboard, FLX-induced anxiety/emotionality-like behaviors. As expected, FLX treatment was endowed with anorectic effects and reduced body weight gain. Altogether, our study shows that short-term FLX treatment results in physiological, neuroendocrine and behavioral stress-like effects in adolescent male rats. More importantly, considering that the AVP- and 5-HTergic systems: (1) are intimately involved in regulation of the stress response; (2) are regulated by sex hormones and (3) are related to regulation of aggressive behaviors, our results highlight the potential significance of these systems mediating the anxiogenic/emotionality/stress-like responses of adolescent male rats to short-term FLX treatment.

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Acknowledgments

This work has been supported by the grant SAF2005-05738 from the “Ministerio de Educación y Ciencia” of the Spanish Government. We are grateful to Thomas C. Moore and Rocío Naveiras Cabello for their technical support.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), Madrid, Spain

    Francisca Gomez & Luis García-García

  2. Brain Mapping Unit, Pluridisciplinary Institute, Universidad Complutense de Madrid (UCM), Paseo Juan XIII, n° 1, 28040, Madrid, Spain

    Francisca Gomez & Luis García-García

  3. Department of Psychobiology, Faculty of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain

    César Venero

  4. Department of Animal Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense de Madrid (UCM), Madrid, Spain

    María-Paz Viveros

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  1. Francisca Gomez
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  2. César Venero
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  3. María-Paz Viveros
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  4. Luis García-García
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Correspondence to Francisca Gomez.

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Gomez, F., Venero, C., Viveros, MP. et al. Short-term fluoxetine treatment induces neuroendocrine and behavioral anxiogenic-like responses in adolescent male rats. Exp Brain Res 233, 983–995 (2015). https://doi.org/10.1007/s00221-014-4173-9

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