Identification of stable individual variation in learning of drug-associated cues in mice




Shetty, Ritu
Wagner, Alison
Forster, Michael


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Hypothesis/Purpose/Objective: Conditioned place preference (CPP) is a behavioral assay used to assess learning of drug-associated cues and drug reward. Though the reliability of the assay is established, considerable variability exists when examining the outcome of conditioning in individual mice. Indeed, at doses expected to produce robust CPP, some mice exhibit weak preference, or even aversion. The present study characterized the reliability and stability of these CPP phenotypes (i.e. robust, weak, or averse) to determine if they represent true individual differences. These phenotypes were investigated using the psychostimulants d-amphetamine and methylenedioxypyrovalerone (MDPV), as recent studies and trends in drug use suggest that synthetic cathinones, such as MDPV, have a high potential for abuse. Materials/Methods: The CPP phenotypes were examined in subsets of two hundred fifty-two male Swiss-Webster mice used in dose-response studies, in which separate groups received either saline, MDPV, or d-amphetamine. These groups were subsequently assessed for conditioned place preference. One post-test was conducted at 24 hours after the initial test in a group receiving 2.5 mg/kg d-amphetamine. Three post-tests were conducted at 24, 48, and 72 hours after the initial test in groups receiving 10 mg/kg MDPV and 0.5 mg/kg d-amphetamine. At the initial test session, outcome of conditioning was examined by calculating a preference score; higher preference score indicated greater learning. Pearson’s r was used to analyze the relationship between place preference during the test and the post-tests. An Analysis of Variance was used to ensure the partitioning criteria were appropriate and the phenotypes were, in fact, separate groups. Results: When examining preference scores, three distinct phenotypes emerge. Data from groups receiving 10 mg/kg MDPV and 0.5 and 2.5 mg/kg d-amphetamine demonstrate a strong correlation between the initial test and the post-test(s). Conclusions: Outbred mice exhibit differential conditioning to psychostimulants, a phenomenon that can be qualified by distinct phenotypes. These phenotypes are stable over additional post-tests, as mice seem to persist in the phenotype they exhibit during the initial test. Taken together, these results suggest robust individual differences in the development of place preference.