TY - JOUR
T1 - Rats classified as low or high cocaine locomotor responders
T2 - A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors
AU - Yamamoto, Dorothy J.
AU - Nelson, Anna M.
AU - Mandt, Bruce H.
AU - Larson, Gaynor A.
AU - Rorabaugh, Jacki M.
AU - Ng, Christopher M.C.
AU - Barcomb, Kelsey M.
AU - Richards, Toni L.
AU - Allen, Richard M.
AU - Zahniser, Nancy R.
N1 - Funding Information:
The authors acknowledge the generous support by NIDA : R37/R01 DA004216 , K05 DA015050 , F30 DA024948 , F31 DA023343 , and F31 DA027277 and by NIGMS : T32 GM007635 .
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - Cocaine conditioned place preference
KW - Cocaine self-administration
KW - Cocaine sensitization
KW - Dopamine clearance
KW - Dopamine transporter
KW - Dopamine uptake
KW - Drug discrimination
KW - Individual differences to cocaine
KW - Locomotor activity
KW - NMDAR phosphorylation
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U2 - 10.1016/j.neubiorev.2013.07.002
DO - 10.1016/j.neubiorev.2013.07.002
M3 - Review article
C2 - 23850581
AN - SCOPUS:84880936877
SN - 0149-7634
VL - 37
SP - 1738
EP - 1753
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
IS - 8
ER -