Individual differences in cocaine-induced locomotor activity in male Sprague-Dawley rats and their acquisition of and motivation to self-administer cocaine.
BACKGROUND
Factors that increase an individual's susceptibility to cocaine dependence remain largely unknown. We have previously shown that adult outbred male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on their locomotor activity following the administration of a single dose of cocaine (10 mg/kg, i.p.). Furthermore, LCR/HCR classification predicts dopamine transporter function/inhibition, cocaine-induced locomotor sensitization, and cocaine-conditioned place preference.


OBJECTIVE
The present study assessed LCR/HCR classification and the development of locomotor sensitization on the latency to acquire cocaine self-administration and motivation to self-administer cocaine.


RESULTS
LCRs and HCRs did not differ in their latency to acquire low-dose cocaine self-administration (0.25 mg/kg/infusion over 12 s, fixed ratio 1 schedule of reinforcement). In a follow-up experiment, repeated experimenter-administered injections of cocaine (10 mg/kg, i.p.) resulted in locomotor sensitization for LCRs, but not HCRs; nonetheless, all rats exhibited decreased latency to acquire cocaine self-administration compared to the first experiment. Repeated cocaine preexposure and LCR/HCR classification predicted break point when rats responded for cocaine under a progressive ratio schedule of reinforcement (0.25, 0.5, and 1.0 mg/kg/infusion; multiple exposure>single exposure, LCR>HCR), but there was no interaction between these variables.


CONCLUSIONS
Although LCR/HCR classification did not predict the rate of acquisition of cocaine self-administration under these conditions, LCR rats demonstrated greater responding for cocaine after acquisition (PR). Thus, these findings demonstrate the relevance of using the LCR/HCR model when studying susceptibility to cocaine dependence.
Mandt
Bruce H
BH
Department of Pharmacology, University of Colorado Denver, Aurora, CO, USA. Bruce.Mandt@uchsc.edu
Schenk
Susan
S
Zahniser
Nancy R
NR
Allen
Richard M
RM
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015984:Causality; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D007206:Individuality; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012984:Software
D003042:Cocaine