Conditioned Place Preference Paradigm

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. 

Male Sprague-Dawley rats weighing 250-300 g are used for these studies. When drugs are to be administered intracerebroventricularly, rats are anesthetized with 60 mg/kg i.p. sodium hexobarbital and 23 gauge guide cannulae aimed at the lateral ventricle (AP = -0.9 mm, L = +1.5 mm, DV = 3.5 mm) (Paxinos and Watson 1982) are stereotaxically implanted conditioning commences one week later. 

The apparatus consists of 30 x 60 x 30 cm plexigas boxes with a clear Plexiglas front. For conditioning sessions, each box is divided into two equal-sized compartments by means of a sliding wall. One compartment is white with a textured floor, the other black with a smooth floor. For testing, the central wall is raised 12 cm above the floor to allow passage from one compartment to the other. 

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). 

In addition to place preference, others (Mucha and Herz 1985 Broadbentetal. 2002) used taste preference conditioning. 

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The conditioned place preference paradigm is widely used in order to measure the rewarding properties of drugs of abuse (secondary reinforcement). In general individuals are subsequently injected with either the drug or vehicle solution and placed into boxes with... 

Tzschentke, T.M. Measuring reward with the conditioned place preference paradigm a comprehensive review of drug effects, recent progress and new issues. Prog. Neurobiol. 56 613, 1998. 

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... 

Bals-Kubik R, Ableitner A, Herz A, Shippenberg TS (1993). Neuroanatomical sites mediating the, motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. J Pharmacol Exp Ther 264 489-495 Maldonado R, Rodriguez de Fonseca F (2002) Cannabinoid addiction behavioral models and neural correlates. J Neu-rosci 22 3326-3331... 

Using the conditioned place preference paradigm, Mamoon et al. (1995) assessed the rewarding properties of butorphanol in comparison to morphine after unilateral microinjections into the ventral tegmental area of male Lewis rats. 

Sufka (1994) recommended the conditioned place preference paradigm as a novel approach for assessing effects of opioids in chronic pain induced in rats by... 

Sufka KJ (1994) Conditioned place preference paradigm a novel approach for analgesic drug assessment against chronic pain. Pain 58 355-366... 

Another way of demonstrating the rewarding effects of drugs in animals is the conditioned place preference paradigm, in which an animal learns to approach an environment in which it has previously received a rewarding stimulus. Rats had a positive THC place preference after doses as low as 1 mg/kg (41). 

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. 

Hiroi, Noboru, and Norman M. White. 1990. "The Reserpine-Sensitive Dopamine Pool Mediates (+ -Amphetamine-Conditioned Reward in the Place Preference Paradigm." Brain Research 510 33-42. 

In D2 KO mice conflicting results have been obtained on a place preference paradigm. In morphine-naive mice Maldonado et al. (1997) reported an impairment of morphine-conditioned place preference while Dockstader et al. (2001) did not. Curiously morphine-conditioned place preference was impaired in morphine-dependent D2 KO mice. 

Behavioural and neurochemical studies have now clarified the controversy about the abuse liability of cannabinoids by demonstrating that such drugs fulfil most of the common features attributed to compounds with reinforcing properties. Cannabinoid rewarding properties have been identified using intracranial selfstimulation, conditioned place preference and intravenous self-administration paradigms. Furthermore, a cannabinoid withdrawal syndrome has also been characterized in different animal species (Lichtman and Martin 2002 Maldonado and Rodriguez de Fonseca 2002). 

Tzschentke T (2007) Measuring reward with the conditioned place preference (CPP) paradigm update of the last decade. Addict Biol 12(3 ) 227-462. 

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