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Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

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Abstract

Rationale

Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE.

Methods

Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2 mg/kg) or saline-treated conditions, with injections every other day for 15 days. Fourteen days later, all animals received an amphetamine challenge (1 mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed.

Results

PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (medial prefrontal cortex (mPFC)) compared to controls.

Conclusions

PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD.

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Acknowledgments

We would like to thank Linda Ellis who developed the IHC protocol for DA-R expression, Wayne Yu for technical support with RIAs, Nikki Kitay, Farinaz Poursoltani, and Andrew Choe for their valuable assistance with data collection and brain slicing, Stephanie Lieblich for her technical support with IHC, and Dr. Douglas Allan and Luba Veverytsa at the Facility for Synaptic Imaging at the University of British Columbia for training and access to their confocal microscope for imaging of dopamine receptors. This research was funded by grants from the Canadian Foundation for Fetal Alcohol Research (CFFAR) to JW and LAMG, and NIH/NIAAA R37 AA007789 to JW. LAMG is also supported by grants from CIHR, NSERC and Alzheimer’s Society for Canada. KAU was funded by IMPART (CIHR STIHR Training Program) and grant support.

Disclosure statement

No financial support from any individual or corporate body has been received for compensation of work; therefore, the authors declare no potential conflict of interest.

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Authors and Affiliations

  1. Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada

    Kristina A. Uban, Joanne Weinberg & Liisa A. M. Galea

  2. Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

    Joanne Weinberg & Liisa A. M. Galea

  3. Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    Wendy L. Comeau, Tamara Bodnar, Wayne K. Yu & Joanne Weinberg

Authors
  1. Kristina A. Uban
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  2. Wendy L. Comeau
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  3. Tamara Bodnar
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  4. Wayne K. Yu
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  5. Joanne Weinberg
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  6. Liisa A. M. Galea
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Correspondence to Kristina A. Uban, Joanne Weinberg or Liisa A. M. Galea.

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Joanne Weinberg and Liisa A. M. Galea are equal senior authors.

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Uban, K.A., Comeau, W.L., Bodnar, T. et al. Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats. Psychopharmacology 232, 1705–1716 (2015). https://doi.org/10.1007/s00213-014-3804-y

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  • DOI: https://doi.org/10.1007/s00213-014-3804-y

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