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Effects of prenatal immune activation and peri-adolescent stress on amphetamine-induced conditioned place preference in the rat

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Abstract

Rationale

Addiction is a disease of learning and memory, as learning processes underlying acquisition, extinction, and reinstatement of drug-paired associations play central roles in addiction. Early developmental stress enhances risk for drug problems in adulthood. Environmental factors influencing learning and memory processes relevant to addiction remain incompletely characterized.

Objectives

To determine effects of prenatal immune activation and developmental stress on conditioned place preference to amphetamine, and reversal learning.

Methods

Pregnant Sprague-Dawley rats were injected with polyinosinic:polycytidylic acid (poly I:C) or vehicle on gestational day 14. Half of the male offspring received 2 h of restraint stress at post-natal day 35. Behavioral testing was performed in adulthood.

Results

Restraint stress inhibited acquisition of place preference to low-dose amphetamine (0.5 mg/kg), while poly I:C treatment had no measurable effect on place preference acquisition. In contrast, drug-induced reinstatement of preference for drug-paired chamber was enhanced in offspring of poly I:C-treated dams [F(1,25) = 5.31, p = 0.03]. Performance on a Morris water maze reversal learning task was impaired in poly I:C offspring. Reversal learning performance was correlated with place preference reinstatement in non-stressed (r 2 = 0.42, p = 0.0095), but not stressed rats (r 2 =0.04, p = 0.49).

Conclusions

Prenatal immune activation enhances drug-induced reinstatement of conditioned place preference. These data demonstrate longstanding impact on behaviors with potential influence on risk for drug relapse as a consequence of prenatal immune activation. Further study is needed to determine clinical and epidemiological consequences of similar exposures in human populations.

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Acknowledgements

This work was supported by the Department of Veterans Affairs Medical Research Service and National Institute of Mental Health (R21MH083192-01). The experiments described in this manuscript comply with the current laws of the USA. The authors disclose the following relationships which might potentially bias this work: Neil M. Richtand: Consultant: Bristol-Meyers Squibb, Gerson Lehrman Group, Sunovion Pharmaceuticals Inc./Sepracor. Speaker’s Bureau: Bristol-Meyers Squibb, Otsuka America Pharmaceutical, Schering–Plough Corporation/Merck, Novartis Pharmaceuticals, Sunovion Pharmaceuticals Inc./Sepracor. Grant/Research Support: Ortho-McNeil Janssen Scientific Affairs, LLC; AstraZeneca Pharmaceuticals.

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Authors and Affiliations

  1. Psychiatry Service (V116A), Cincinnati Veterans Affairs Medical Center, 3200 Vine Street, Cincinnati, OH, 45220, USA

    Neil M. Richtand, Rebecca Ahlbrand & Paul S. Horn

  2. Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA

    Neil M. Richtand, Rebecca Ahlbrand, Brad Chambers, Jon Davis & Stephen Benoit

  3. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH, 45267, USA

    Neil M. Richtand & Stephen Benoit

  4. Department of Mathematical Sciences, University of Cincinnati, Cincinnati, OH, 45221, USA

    Paul S. Horn

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  1. Neil M. Richtand
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Correspondence to Neil M. Richtand.

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Richtand, N.M., Ahlbrand, R., Horn, P.S. et al. Effects of prenatal immune activation and peri-adolescent stress on amphetamine-induced conditioned place preference in the rat. Psychopharmacology 222, 313–324 (2012). https://doi.org/10.1007/s00213-012-2646-8

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