Original Investigation


, Volume 173, Issue 1, pp 41-48

First online:

Effects of periadolescent versus adult cocaine exposure on cocaine conditioned place preference and motor sensitization in mice

  • Nicole L. Schramm-SapytaAffiliated withDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center
  • , Adeola R. PrattAffiliated withDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center
  • , Danny G. WinderAffiliated withDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical CenterCenter for Molecular Neuroscience and John F. Kennedy Center for Research on Human Development, Vanderbilt University Medical Center724B Robinson Research Building, Vanderbilt University Medical Center Email author 

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Age of initial exposure to addictive substances is inversely proportional to risk of developing drug dependence. There is debate, however, as to whether intake at a young age causes dependency or whether young people who experiment with addictive substances are predisposed to dependency by other factors.


We tested the relationship between cocaine exposure at two different ages in mice and the development of subsequent drug-seeking behavior to test for age-specific exposure effects.


We performed dose-response analysis of cocaine conditioned place preference (CPP) and locomotor activity in periadolescent and adult C57Bl/6J mice. In addition, we pretreated periadolescent and adult C57Bl/6J mice with cocaine or saline in the home cage or a drug-associated context, and then examined their behavior in a biased CPP procedure in adulthood.


Dose-response relationships were similar between the two age groups. In the pretreatment experiments, we observed locomotor sensitization during the pretreatment in periadolescent but not adult mice. We also observed an enhanced aversion to the non-preferred side of the chamber in periadolescent mice compared to adult mice, which was alleviated by cocaine association with that side. Third, we observed that after further conditioning in adulthood, there were no pretreatment-specific effects.


Our results are consistent with a “vulnerable brain” hypothesis for responses to cocaine based on our findings that periadolescent mice exhibit greater locomotor sensitization to cocaine, and greater baseline anxiety responses that are alleviated by cocaine exposure compared to adult mice.


Cocaine Development Adolescent Mouse Conditioned place preference Addiction