The Conditioned Place Preference Model

Quantify context-driven behavioral responses to drug exposure

The conditioned place preference (CCP) model has been used for decades to evaluate a drug’s abuse liability and its potential to treat substance use disorder (SUD). In this paradigm, animals learn to associate a specific environment with drug exposure, and preference for that environment is later measured as an indicator of reward.

A Behavioral Model with Decades of Use in Addiction Research

Conditioned place preference originated from early place-conditioning studies in the mid-20th century and was formalized in the 1970s as researchers began pairing drug exposure with distinct environments to measure learned behavioral responses. 

Our conditioned place preference model builds on this well-established paradigm using a biased, two-chamber design in rats to generate clear, reproducible behavioral readouts. This approach enables sensitive detection of both rewarding and aversive effects across a range of compounds, including opioids, supporting early assessment of abuse liability in preclinical development.

In addition to its classical use, the conditioned place preference model is increasingly applied to evaluate therapies for SUD. By measuring whether a test article reduces or blocks drug-induced preference, researchers can assess its potential to modulate drug-seeking behavior. 

Melior offers optional locomotor activity tracking during conditioning and test sessions, which provides additional context, helping distinguish true reward-driven effects from stimulant or sedative influences and strengthening overall data interpretation.

Advantages of the Conditioned Place Preference Model

  • Generate robust behavioral readouts of drug reward and aversion
  • Collect locomotor activity during conditioning and test sessions to support data interpretation
  • Compare opioid-induced CPP across compounds to assess relative abuse liability
  • Timelines as short as 2 weeks to complete typical opioid CPP in-life studies

Ready to get started or looking for a custom model?

We offer customizable conditioned place preference model studies, with flexible conditioning timelines, protocols, compound classes, and endpoints tailored to your research goals.

  • We chose Melior Discovery because they were responsive and cost effective.  We are staying with them as a chosen scientific partner because of their thoughtful scientific input to experimental design and attention to detail.  Their expertise and flexibility allowed us to quickly adapt the study design and evaluate additional outcome measures to pursue unexpected activity.

    Sridharan Rajamani, Ph.D., Senior Research Scientist

    Gilead Sciences
  • I have been working with Melior on a number of projects over the course of a few years now.  They have been a great partner throughout this time.  The scientists whom I have worked with have been great problem-solvers and were customer focused.

    Jay Lichter

    Avalon Ventures
  • Melior provided State-of-the-art Preclinical Pharmacology Support for a period of nearly a year where a series of in vivo studies were completed on a weekly basis. The staff was extremely user-friendly and the operational processes were excellent. I can recommend Melior without reservation.

    Richard DiMarchi, PhD

    Cox Professor of Chemistry & Gill Chair in Biomolecular Sciences Indiana University, Department of Chemistry
  • Because Melior could do the orthotopic intracranial implants, we were able to do survival studies with brain tumor-bearing animals that were treated with our therapy, showing a beautiful survival with our agent versus control. Talk about something that gets your investors going! These beautiful survival curves with our agent versus control and visual photos are in all of our investor decks because… it's powerful.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Melior works in many therapeutic areas, like CNS, inflammatory disease, GI, cardiovascular, and oncology. I was very pleased that when it came to doing tumor studies, both subcutaneous and intracranial, they did them well. They reported on the studies on time and did the data analysis really well.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Their areas of expertise are extensive, and they are very experienced, responsive, and flexible in terms of how the study is run. Their pricing is reasonable, making them the best option for a young, not well-funded company like ours.

    Maxine Gowen

    Tamuro Bio
  • Melior’s team was very experienced and knowledgeable. They were always very open to suggestions and questions, spending a lot of time helping us feel comfortable with the study design. I would give them very high marks.

    Maxine Gowen

    Tamuro Bio
  • The most important factors in choosing to work with Melior were the fit between the tests they could run and our needs, as well as their tight budget and proximity. Melior was the best fit for our research goals.

    Ira Spector

    SFA Therapeutics
  • Melior was able to do exactly what we needed essentially flawlessly... They communicated the data really well with regular updates—they became an extension of us. If you're looking for a US-based CRO that can do good quality work, produce an excellent work product, is going to be very responsive to your needs, can accommodate changes in study plans, and keep you in the loop, go with Melior. Talk about something that gets your investors going! They showed these beautiful survival curves with our agent versus control, and visual photos are in all of our investor decks because... it's powerful.

    Bruce Ruggeri, Ph.D., VP Pharmacology, Modifi Bio

  • The most important value inflection point in a drug development program, apart from initial clinical proof-of-concept, is the first in vivo proof-of-concept. We get that. So, we pour our energies into providing the best study outcomes for every project. Ultimately, Modifi Bio's success is also Melior's.

    Andrew Reaume, Ph.D., President & Co-founder, Melior Discovery

percent time in zone Figure 1

Figure 1. Expression of Conditioned Place Preference (CPP) on Day 10 (test day). Animals were trained to test compounds for 4 days. On the test day, no compounds were administered. The figure represents the percent of time spent in the drug-paired chamber versus the saline-paired chamber. Saline or Naltrexone (1, 3, or 10mpk) was administered 30 minutes prior to saline or morphine (5mpk) administration on conditioning days.

percent time in zone figure 2

Figure 2. Expression of Conditioned Place Preference (CPP) on Day 10 (test day). Animals were trained to test compounds for 4 days. On the test day, no compounds were administered. The figure represents the percent of time spent in the drug-paired chamber versus the saline-paired chamber. Saline or Naltrexone (3mpk) was administered 30 minutes prior to saline or oxycodone (3mpk) administration on conditioning days.

Publications

Ma K, Pham T, Wang J, O-Sullivan I, DiCamillo A, Du S, Mwale F, Farooqui Z, Votta-Velis G, Bruce B, van Wijnen AJ, Liu Y, Im HJ. Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage. Sci Adv. 2024 Feb 16;10(7):eadi5501. doi: 10.1126/sciadv.adi5501. Epub 2024 Feb 14. PMID: 38354243; PMCID: PMC10866538.

Frequently Asked Questions

What is conditioned place preference (CPP), and what does it measure in behavioral research?

Conditioned place preference (CPP) is a behavioral assay used to evaluate how animals associate a specific environment with drug exposure. It measures whether a compound produces rewarding or aversive effects by assessing the amount of time an animal spends in a drug-paired environment. CPP is widely used to assess abuse liability and to evaluate compounds that may reduce drug-associated preference in substance use disorder (SUD) research.

What does “conditioning preference” mean in the context of conditioned place preference studies?

In CPP studies, “conditioning preference” refers to the learned association between a drug’s effects and a specific environment. During conditioning, animals are exposed to a compound in one chamber and a control condition in another. If the compound is rewarding, animals will later spend more time in the drug-paired chamber, indicating a conditioned preference.

What are the limitations of the conditioned place preference model?

While the conditioned place preference model is a well-established tool for assessing reward-related behavior, it does not measure active drug-taking or reinforcement directly, as seen in self-administration models. Results can also be influenced by factors such as locomotor effects or initial chamber bias, which is why additional data, such as locomotor activity, can be useful for interpretation. 

Despite these limitations, CPP remains a valuable and widely used approach for evaluating abuse liability and substance use disorder mechanisms.

Citations

Rossi, N.A., Reid, L.D. Affective states associated with morphine injections. Psychobiology 4, 269–274 (1976). https://doi.org/10.3758/BF03332869