RAT CONDITIONED PLACE PREFERENCE (CPP)

Animals

Studies are conducted in adult male and female Sprague Dawley rats (Envigo) in an AAALAC-accredited facility with approval from an Institutional Animal Care and Use Committee, and implemented in accordance with the Guide for the Care and Use of Laboratory Animals 8th Edition (National Research Council, 2011) with standards set by the National Institutes of Health.

Experimental procedure

Conditioned place preference (CPP) is commonly used to measure the rewarding properties of an asset in laboratory animals. A typical study involves pairing a stimulus of interest (e.g., food or compound) with a distinct environmental context (e.g., tactile, visual, and/or olfactory). Following conditioning, a bias to the stimulus-paired context relative to control indicates that the stimulus was rewarding.

The CPP test is conducted in appropriate group sizes determined by power analysis. Male and female rats (n=10-20) are evaluated in separate cohorts. Multiple doses are investigated, and vehicle and positive control groups are included to establish the validity of the experiment. For all animals, experimenters are blinded to the treatments, and dosing is performed by an independent experimenter.

CPP study design

During the CPP testing, rats are placed in a divided arena as presented in Figure 1.

The CPP trials are videotaped, and the time spent in each chamber is scored by two independent experimenters blinded to the study design. The CPP study design spans through 10 days, based on Kimmel et al., 2000, as follows:

Baseline preference assessment (Day 1): rats are free to explore the entire testing area freely for 20 minutes and the time spent in each chamber is recorded. Rats with strong preference for one chamber are excluded.

Conditioning (Days 2 to 9): on experimental days 2, 4, 6, and 8, rats are treated with vehicle and confined to one chamber for 20 minutes. On experimental days 3, 5, 7, and 9, rats are treated with the asset and are confined to the other chamber for 20 minutes. For each study, the chambers are paired with the asset or the vehicle in a counterbalanced manner.

Post-conditioning bias test (Day 10): post-conditioning testing is conducted in the absence of the stimulus (i.e., without asset or vehicle administration). Rats are allowed to explore the testing arena freely for 20 minutes, with the door open, and the time spent in each chamber is recorded.

Results are expressed as the percent of time the rat spend in the compound compartment on days 1 and 10. Results are also expressed as preference score, defined as the difference of time (seconds) in the compound-paired compartment from the time in the vehicle-paired compartment.

This work was conducted by PsychoGenics Inc. (Paramus, NJ) in collaboration with PSPP, NINDS, NIH under contract # 75N95019D00026