Simultaneous expression of cocaine-induced behavioral sensitization and conditioned place preference in individual rats

Abstract

Conditioned place preference and locomotor sensitization are rodent behavioral models commonly used to investigate the actions of drugs of abuse. However, few studies have examined both paradigms in the same group of animals. We were interested in developing a combined protocol which successfully induced both conditioned place preference and sensitization simultaneously in cocainetreated Sprague Dawley rats in order to test the hypothesis that the magnitude of these two phenomena would be positively correlated. We used an open-field with a removable place preference insert to assess these measures independently. Cocaine-conditioned animals demonstrated a significant shift in preference for the drug-paired compartment and a sensitized locomotor response which was not observed in saline-conditioned animals challenged with cocaine. There was no significant relationship between locomotor sensitization and conditioned place preference in individual animals. We further examined these results with respect to each rats' initial response to cocaine, response to a novel environment and central zone entries in an open-field. Locomotor sensitization demonstrated an inverse correlation with the initial cocaine response. In contrast, conditioned place preference demonstrated an inverse correlation with the centre response. These results demonstrate that the combination of the acute cocaine response and the centre response in a novel open field environment can be used to indicate the propensity of a given rat to exhibit either behavioral sensitization or conditioned place preference; however, it seems that sensitization and place preference are not necessarily co-expressed to a similar extent in the same individual animal.

Cyclin-Dependent Kinase Inhibitor 1a (p21) Modulates Response to Cocaine and Motivated Behaviors

“…Wild-type mice again acted similarly in response to cocaine as rats during the CPP assay (Seymour and Wagner, 2008). Both cocaine-treated wild-type and p21 2/2 mice spent significantly more time in the designated drug-paired compartment during the CPP post-test than during the pretest (wild-type: t 5 2.758, df 5 22; knockout: t 5 5.991, df 5 22; Fig.…”

“…We first verified that wild-type mice respond to cocaine similarly to rats in a behavioral protocol that combines locomotor activity and CPP assessments in the same animal (Seymour and Wagner, 2008). Cocaine-treated wild-type mice exhibited increased locomotor activity postinjection (15 mg/kg i.p.)…”

“…The experimental design for the mouse behavior assays was based on that described in previous studies (Seymour and Wagner, 2008). For the place preference assay, mice were first tested in a pretest session (day 1) in which each was placed in the lighter/grid floor compartment and the guillotine door was removed, allowing free access to both compartments for 15 minutes.…”

Temporal and dose-dependent differences in simultaneously-induced cocaine hypervigilance and conditioned-place-preference in marmoset monkeys

“…Furthermore, the CPP response can be potentiated in previously sensitized individuals (Shippenberg and Heidbreder, 1995), while the expression of sensitized behaviors may be controlled by conditioned environmental stimuli (Mattson et al, 2008). However, the two aspects are rarely evaluated simultaneously in the same individual, with reports only for rodents (Orsini et al, 2005;Seymour and Wagner, 2008;Shimosato and Ohkuda, 2000). Their CPP behavior and locomotor sensitization were not coexpressed to the same extent in the same animal (Brabant et al, 2005;Orsini et al, 2005;Seymour and Wagner, 2008).…”

Aberrant approach-avoidance conflict resolution following repeated cocaine pre-exposure

“…Moreover, there is much behavioral evidence that prior repeated stimulant drug exposure enhances positive incentive motivation. For example, rodents with a history of cocaine exposure show enhanced acquisition of conditioned place preference for cocaine-reinforced locations (Lett 1989;Seymour and Wagner 2008) and decreased latency values to obtain cocaine reward in a runway task (Deroche et al 1999). Similarly, rodents with a history of amphetamine exposure show enhanced Pavlovian conditioning to instrumental transfer for sucrose reinforcement (Wyvell and Berridge 2001), enhanced conditioning for cues predictive of sucrose reinforcement (Harmer and Phillips 1998), and enhanced sexual pursuit behaviors (Fiorino and Philips 1999).…”