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

Anna K. Radke, Nathan A. Holtz, Jonathan C. Gewirtz, Marilyn E. Carroll

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
Issue number1
StatePublished - May 2013

Bibliographical note

Funding Information:
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).


  • CPA
  • Morphine
  • Rat
  • Saccharin preference
  • Selective breeding
  • Startle
  • Withdrawal


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