Conditioned Place Preference Test

On the 9th day, in the absence of any treatment, the animals have free access to both compartments via the guillotine doorway which is left open and the session is monitored and recorded on videotape. The time spent by the animal in each of the two compartments 

Twelve animals are studied per group. The experiment is performed blind. 

The test substance is usually evaluated at 2 doses and compared with a vehicle-treated control group. 

During the conditioning phase itself, where the animal in confined to one or the other compartment, no behavioral monitoring is undertaken. 

The measure of time spent in each compartment on the test day (Day 9) in the absence of the test substance is an indication of the animal s preference for each compartment. Measures of the number of crossings provide an indication of the animal s spontaneous level of activity under the conditions of the test. It should be noted that crossings are not an indication of the effects of the test substance on locomotion, because the animal is not under the influence of the test substance during the test. Clear decreases in the number of crossings are, nonetheless, systematically observed on the test day after previous conditioning with substances such as morphine, and therefore appear to be part of the conditioned place preference process. On the other hand, no ready interpretation can be offered for these changes. 

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Even more importantly, URB597 seems to lack hedonic properties, as it had no effect on two rat models of abuse potential, the conditioned place preference test and the drug discrimination test (Kathuria et al., 2003). Similar results have been recently obtained also in experiments with monkeys (Justinova et al., 2008). 

Takeda M, Sawano S, Imaizumi M, Fushiki T (2001b) Preference for com oil in olfactory-blocked mice in the conditioned place preference test and the two-bottle choice test. Life Sci... 

Conditioned place preference appears to provide a fairly simple indication of whether a test substance exerts positive reinforcing effects. The existence of conditioned place preference with a novel substance therefore represents a clear first sign of abuse potential. 

On the other hand, absence of conditioned place preference cannot be taken to indicate that the test substance is devoid of abuse potential. Indeed, the main weakness of the conditioned place preference paradigm is that several known substances of abuse... 

The conditioned place preference paradigm has been used widely to examine behavioral actions that are thought to be related to positive reinforcing effects as measured by other procedures, such as self administration (van der Kooy 1987 Hoffman 1989 Tzschenke 1998 Self and Stein 1992). Particular environmental stimuli are paired with the presence or absence of a presumed reinforcer (e.g. drug or food) and later, in the absence of that reinforcer, animals are tested for their preference for either environment. 

Fig. 3. Effect of NAc shell and core DA D2 receptor blockade on acquisition of morphine-conditioned place preference. L-sulpiride (12.5, 25.0 and 50.0 ng/ side), or saline were infused into the NAc shell (upper panel) and core (bottom panel) 10 min before morphine (1 mg/kg s.c.). Each bar represents mean SEM of the difference (in seconds) between the time spent in the drug-paired compartment on the testing day and the time spent in this compartment in the preconditioning session. P < 0.05 versus saline s.c. of the corresponding control group p < 00.5 versus saline i.c. plus morphine s.c.

The development of some of the secondary models such as conditioned place preference and electrical brain stimulation which do not require intravenous drug injections will continue to occur (for complete descriptions of the conditioned place preference paradigm and validation data, see Bardo and Bevins (2000) or Cunningham et al. (2006, 2011) for a complete description of the electrical brain stimulation model, also see O Neill and Todtenkopf (2010) or McBride et al. (1999)). A better understanding of the predictivity of these models and correlation with the traditional self-administration model will be required for these models to assume a mainstream position in abuse potential assessment. The self-administration model s predictive correlation to abuse potential in humans has been well characterized but new models will have to be characterized and published to have equal impact in future abuse potential testing. 

Fig. 3. Comparison of METH-induced CPP in single histamine receptor gene knockout mice. Mice were injected 1 mg/kg of METH or saline every other day, and confined for 30 min to a compartment designed to condition the place preference. The CPP score were calculated using the staying time of mouse in each compartment for 15 min before and after the conditioning. Each value represents the mean S.E.M. of 6-18 mice. Statistical analysis was performed by means of one-way ANOVA followed by Tukey s test ( p < 0.05, p < 0.01).

In order to distinguish place preference and place aversion, place conditioning behavior can be expressed by a difference in preference pre and post conditioning, where post and pre values are the difference in time spent in the preferred and the non-preferred sides in the post-conditioning and pre-conditioning tests, respectively. Positive values indicate preference and negative values aversion (Kitaichi et al. 1996). For non-biased procedures, where animals do not show an inherent preference for either compartment, results are presented simply as a difference score (i.e., time spent in the drug-paired compartment minus time spent in the vehicle-paired compartment). 

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