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Reduced emotional signs of opiate withdrawal in rats selectively bred for low (LoS) versus high (HiS) saccharin intake

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Abstract

Rationale

Rats bred for high (HiS) and low (LoS) saccharin intake exhibit divergent behavioral responses to multiple drugs of abuse, with HiS rats displaying greater vulnerability to drug taking. Previous research indicates that this effect may be due to increased sensitivity to reward in HiS rats and to the aversive effects of acute drug administration in LoS rats.

Objective

The current study investigated whether HiS and LoS rats also exhibit different behavioral signs of withdrawal following one or repeated opiate exposures.

Methods

Emotional signs of opiate withdrawal were assessed with potentiation of the acoustic startle reflex and conditioned place aversion (CPA) in male and female HiS and LoS rats. Startle was measured before and 4 h after a 10-mg/kg injection of morphine on days 1, 2, and 7 of opiate exposure. CPA was induced with a 2-day, naloxone-precipitated conditioning paradigm. Somatic signs of withdrawal and weight loss were also measured.

Results

Male and female LoS rats exhibited lower startle potentiation than HiS rats on the seventh day of morphine exposure. LoS male rats also failed to develop a CPA to morphine withdrawal. No differences in physical withdrawal signs were observed between HiS and LoS rats, but males of both lines had more physical signs of withdrawal than females.

Conclusions

These results suggest that LoS rats are less vulnerable to the negative emotional effects of morphine withdrawal than HiS rats. A less severe withdrawal syndrome may contribute to decreased levels of drug taking in the LoS line.

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Acknowledgments

We thank Sofiya Hupalo and Jacob Leslie for technical assistance, Gail Towers for animal husbandry, Dr. Mark Thomas for the use of the place-conditioning apparatus, and Dr. Andrew Harris for assistance measuring somatic withdrawal signs. This work was funded by NIDA grants K05 DA015267 and P20 DA024196 (MEC) and the University of Minnesota (JCG).

Conflict of interest

The authors declare no conflict of interest in regard to this work.

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Authors and Affiliations

  1. Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, USA

    Anna K. Radke, Nathan A. Holtz & Marilyn E. Carroll

  2. Department of Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA

    Jonathan C. Gewirtz

  3. Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA

    Jonathan C. Gewirtz

  4. National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rockville, MD, 20852, USA

    Anna K. Radke

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  1. Anna K. Radke
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Correspondence to Anna K. Radke.

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Radke, A.K., Holtz, N.A., Gewirtz, J.C. et al. Reduced emotional signs of opiate withdrawal in rats selectively bred for low (LoS) versus high (HiS) saccharin intake. Psychopharmacology 227, 117–126 (2013). https://doi.org/10.1007/s00213-012-2945-0

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