期刊
PSYCHOPHARMACOLOGY
卷 201, 期 2, 页码 195-202出版社
SPRINGER
DOI: 10.1007/s00213-008-1265-x
关键词
Cocaine; Locomotor activity; Rat; Self-administration; Sensitization; Reinforcement; Motivation
资金
- NIH [R37 DA004216, F31 DA023343, T32 GM007635, K05 DA015050]
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. 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. 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. 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.
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