Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

Dorothy J. Yamamoto, Anna M. Nelson, Bruce H. Mandt, Gaynor A. Larson, Jacki M. Rorabaugh, Christopher M.C. Ng, Kelsey M. Barcomb, Toni L. Richards, Richard M. Allen, Nancy R. Zahniser

Research output: Contribution to journalReview article

21 Scopus citations

Abstract

Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine's discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors.

Original languageEnglish (US)
Pages (from-to)1738-1753
Number of pages16
JournalNeuroscience and Biobehavioral Reviews
Volume37
Issue number8
DOIs
StatePublished - Sep 2013

Keywords

  • Cocaine conditioned place preference
  • Cocaine self-administration
  • Cocaine sensitization
  • Dopamine clearance
  • Dopamine transporter
  • Dopamine uptake
  • Drug discrimination
  • Individual differences to cocaine
  • Locomotor activity
  • NMDAR phosphorylation

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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