Conditioned place preference
Conditioned place preference is a form of Pavlovian conditioning used to measure the motivational effects of objects or experiences. This motivation comes from the pleasurable aspect of the experience, so that the brain can be reminded of the context that surrounded the "encounter". By measuring the amount of time an animal spends in an area that has been associated with a stimulus, researchers can infer the animal's liking for the stimulus. This paradigm can also be used to measure conditioned place aversion with an identical procedure involving aversive stimuli instead. Both procedures usually involve mice or rats as subjects. This procedure can be used to measure extinction and reinstatement of the conditioned stimulus. Certain drugs are used in this paradigm to measure their reinforcing properties. Two different methods are used to choose the compartments to be conditioned, and these are biased vs. unbiased. The biased method allows the animal to explore the apparatus, and the compartment they least prefer is the one that the drug is administered in and the one they most prefer is the one where the vehicle is injected. This method allows the animal to choose the compartment they get the drug and vehicle. In comparison, the unbiased method does not allow the animal to choose what compartment they get the drug and vehicle in. Instead, the researcher chooses the compartments.
Humans have also been shown to develop conditioned place preferences; for example, people taking therapeutic doses of amphetamine develop a CPP for where they consumed the drug.
The CPP effects of many drugs have been reviewed.
Conditioning procedure
As in Pavlovian conditioning, an initial neutral stimulus, in this case, environmental cues, is repeatedly paired with an unconditioned stimulus that naturally produces a response prior to conditioning. Over time and pairings, the neutral stimulus will come to elicit responses similar to the unconditioned response. In conditioned place preference, the unconditioned stimulus could be any number of things including food pellets, water, sweet fluid, novel toys, social interaction, drug intoxication, drug withdrawal, foot shock, illness, wheel running or copulation. The initially neutral environmental cues become associated with the motivational properties of the unconditioned stimulus leading to either approach or avoidance of the environment. Often in practice, there is a control and treatment group used to strengthen the ability to make causal claims from the results. The treatment group is administered the unconditioned stimulus while the control group is given saline or nothing to control for all elements of the procedure.Apparatus
The conditioned place preference protocol makes use of an apparatus that contains two or more compartments or areas. These two compartments are designed so that the animal can discriminate between them. Differently patterned walls or floors or different types of floor textures may be used to ensure the animal can discriminate between the compartments.Steps to conditioning place preference or aversion
Conditioned place preference involves three phases: habituation, conditioning, and preference testing.Habituation
In the habituation procedure, the animal is given a chance to explore the apparatus. This is done to reduce the effects of novelty and usually consists of one five-minute trial.Conditioning
In the conditioning phase, the unconditioned stimulus is administered to the animal in the treatment group. In this phase of the procedure the animal is only allowed access to one compartment of the apparatus. This compartment will become associated with the motivational effects of the unconditioned stimulus. The environment will come to elicit an approach or avoidance-withdrawal depending on the nature of the unconditioned stimulus. The conditioning procedure usually consists of eight or more five-minute sessions.Preference testing
In the preference testing phase, the animal is allowed unrestricted access to all compartments of the apparatus. During the test, the time a subject spends in each compartment is measured in seconds. Modern protocols utilize commercial automated tracking systems to measure the time; however, manual measurement is also used. Statistical testing is used to determine whether a significant difference in time is present when compared to either a control group or the pre-conditioning time of the same group. Strength of conditioning is inferred by the magnitude of the difference or in the amount of time taken for the response to show extinction.Outcomes
In the standard conditioned place preference procedure, when the unconditioned stimulus is rewarding, rodents will be more likely to approach the compartment that contains cues associated with it. Alternatively, when the unconditioned stimulus is aversive, rodents will be more likely to escape and avoid the compartment that contains cues associated with it. The timing of presentation of the unconditioned stimulus can determine whether place preference or aversion will be conditioned. For example, in trials testing drugs of abuse, if the animal experiences the initial pleasurable effects of the drug while in the conditioning context, the result will likely be conditioned place preference. However, if the animal is given the drug and then the experimenter implements a sufficient delay so that the animal is experiencing the negative aftereffects of the drug, conditioned place aversion is more likely to occur. The timing of these events can be manipulated by the experimenter in order to condition place preference or avoidance.Advantages and disadvantages
Advantages
There are numerous advantages of the conditioned place preference and aversion protocol. It is methodologically simple and only requires two to three weeks to perform all steps of the procedure. In some cases, conditioning can occur with two stimulus-context pairings. It allows both rewarding and aversive effects to be tested and it provides unique information about the motivational effects of unconditioned stimuli. Although the protocol is most often used with mice and rats, it can be adapted for use in other species such as birds and other rodents.In drug testing the conditioned reward or aversive effects can be tested in a drug-free state where the animals will not be impaired due to drug use. The testing is also sensitive to the effects of low drug doses. Conditioned place preference is well suited to measure the temporal profile of drugs as well as the aversive effects of withdrawal. This can be done by varying the time of drug administration in relation to the presentation of the to-be-conditioned context. The procedure also can be utilized to measure the neural circuits involved in drug reward.
Disadvantages
The conditioned place preference and aversion protocol are subject to several disadvantages and limitations. Perhaps the most significant disadvantage is that despite experimenters' best attempts to habituate animals to the procedure before conditioning, novelty-seeking effects can skew the data. Also, without a clear control of several variables that may interfere with the outcomes, such as the animal's strain, age, weight and housing, results from different studies may be difficult to compare, as the different outcomes may seem to contradict each other.Another limitation of the procedure is the distinction between a biased and an unbiased CPP apparatus. Some authors indicate the importance of declaring in the publication, which type of CPP box has been used. Thus a pretest is needed to define a possibly existing preference for one compartment. In a biased context, it is to show an absolute CPP to the initially non-preferred place. Otherwise, for instance, when anxiolytic drugs are used as the rewarding agent, we can interpret only relative place preference to be derived from the anxiolytic effect of the drug. On the other hand, with a biased design, we can distinguish between the anxiolytic and anti-aversive effects of drugs independently from potential genuine rewarding effects.
In addition, individuals who will be handling animals must be trained to do this consistently so as to minimize stress on the animal. It has been shown that stressful handling in rodents can weaken conditioning.
There is debate over whether or not the results obtained from drug studies can be generalized to drug reward in humans. It has been claimed that since the animal passively receives the drug, it cannot be compared.