Novel approach to data analysis in cocaine-conditioned place preference

Abstract

Only a sub-group of human drug users progress from initial drug-taking to drug addiction. An important aspect of this progression is the influence of the learned association between the effects of the drug and the environment in which it is experienced on continued drug-taking and-seeking. These associations can be modeled using the conditioned place preference (CPP) paradigm, although no current method of CPP analysis allows for identification of within-group variability among subjects. In the present study, we adapted a “criterion” method of analysis to separate “CPP expressing” from “non-CPP expressing” rats, in order to study more directly within-group variability in the CPP paradigm. Male Sprague-Dawley rats were conditioned with cocaine (5, 10, 20 mg/kg) or saline in an unbiased three-chamber CPP apparatus in either a single- or four-trial CPP procedure. A classification and regression tree analysis of time spent in the cocaine-paired chamber established a time of 324 s spent in the cocaine-paired chamber as the criterion for cocaine CPP expression. This criterion effectively discriminated control from cocaine-conditioned rats and was reliable for rats trained in both a single- and four-trial CPP procedure. The criterion method showed an enhanced ability to detect effective doses of cocaine in the single trial procedure and a blockade of CPP expression by MK 212 (0.125 mg/kg) treatment in a sub-group of rats. These data support the utility of the criterion analysis as an adjunct to traditional methods that compare group averages in CPP.

Individual differences in the improvement of cocaine-induced place preference response by the 5-HT2C receptor antagonist SB242084 in rats

“…Recent studies have provided evidence that 5-HT 2C receptors control the expression of cocaine-conditioned behaviors (dela Cruz et al 2009; Liu and Cunningham 2006) Our results, together with previously published studies, suggest a critical role played by 5-HT 2C receptors in improving the expression of cocaine-associated behaviors, perhaps by decreasing thresholds to motivational effects elicited by the environmental cues that were present at the time of cocaine administrations. Of importance, our study provides evidence of a differential role for the 5-HT 2C receptors in the brain of HR and LR rats in the motivational aspects that initiate and maintain cocaine abuse in these animals.…”

Dopamine in the Dorsal Hippocampus Impairs the Late Consolidation of Cocaine-Associated Memory

“…Cocaine doses of 10, 15, or 20 mg/kg were used for the doseresponse experiment, and 20 mg/kg was used for the remaining experiments. An increase in time spent in the cocaine-associated chamber after conditioning was taken as a reflection of the known rewarding properties of cocaine at this dose (Busse and Riley, 2004;dela Cruz et al, 2009;Crooks et al, 2010).…”

A cocaine cue is more preferred and evokes more frequency-modulated 50-kHz ultrasonic vocalizations in rats prone to attribute incentive salience to a food cue

“…An incentive stimulus has the ability to: (1) attract attention and elicit approach towards it, thus biasing choice; (2) reinforce the acquisition of new behaviors; and (3) evoke conditioned motivational states that support reward seeking even when the reward is not present (Berridge and Robinson 2003; Cardinal et al 2002; Everitt et al 2000; Milton and Everitt 2010; Robinson and Flagel 2009; Wyvell and Berridge 2001). There are, however, large individual differences in the extent to which a CS is attributed with incentive salience (Beckmann et al 2011; dela Cruz et al 2009; Flagel et al 2009; Mahler and de Wit 2010; Robinson and Flagel 2009). For example, in rats, if a spatially discrete cue is paired with delivery of food reward, the cue itself becomes attractive, eliciting approach towards it, serves as an effective conditioned reinforcer, and readily reinstates reward seeking behavior only in a subset of rats (Robinson and Flagel 2009; Yager and Robinson 2010).…”