Expression of stable and reliable preference and aversion phenotypes following place conditioning with psychostimulants.

RATIONALE AND OBJECTIVES: Drug-seeking behavior occurs more readily in some individuals than others. This phenomenon is considered in studies of drug self-administration in which high drug-seeking/taking individuals can be identified. In contrast, studies of conditioned place preference (CPP) often involve a random sample of drug-naïve rodents that includes phenotypes not considered relevant to addiction. The main objective of the current studies was to determine if a priori identification of different conditioning phenotypes could improve the validity and sensitivity of CPP expression as a preclinical test for vulnerability to addiction. METHODS AND RESULTS: Analysis of cocaine place conditioning data from 443 Swiss-Webster mice revealed a trimodal distribution with peaks corresponding to means of k = 3 clusters. The cluster means occurred at high, low, or negative preference scores, the latter suggesting a phenotype acquiring conditioned place aversion (CPA). The same clusters were identified in mice conditioned with methamphetamine, MDPV, or amphetamine, and these clusters remained stable and reliable during three additional expression tests spaced at 24 h. A meta-analysis of effect sizes obtained from CPP literature revealed a positively skewed distribution affected by sample size, consistent with the existence of a CPA phenotype within the populations tested. A dopamine receptor antagonist, flupentixol, blocked cocaine CPP expression in a group containing all phenotypes, but sensitivity improved markedly when CPA phenotypes were excluded from the dataset. CONCLUSIONS: These studies suggest that taking phenotype into consideration when designing place conditioning studies will improve their application as a preclinical tool in addiction biology and drug discovery.

The comparison of acute high-intensity interval exercise vs. continuous moderate-intensity exercise on plasma calprotectin and associated inflammatory mediators.

PURPOSE: Calprotectin promotes the release of inflammatory mediators (e.g., monocyte chemoattractant protein-1 [MCP-1] and myeloperoxidase [MPO]) during the innate immune response as a mechanism to augment leukocyte chemotaxis and phagocytosis. Although plasma calprotectin is elevated with traditional continuous moderate-intensity exercise (CME) as an indicator of the inflammatory response, high-intensity interval exercise (HIIE) has been shown to attenuate systemic inflammation while providing similar improvements in cardiovascular health. Therefore, the purpose of this study was to compare plasma levels of calprotectin, MCP-1, and MPO between acute HIIE vs. CME. METHODS: Nine healthy males (24.67±3.27yrs) were recruited to participate in HIIE and CME on a cycle ergometer. HIIE consisted of 10 repeated 60s of cycling at 90% max watts (Wmax) separated by 2min of active recovery intensity of interval exercise, whereas CME consisted of 28min of cycling at 60% Wmax. Blood samples were collected prior to, immediately post, and 30 and 60min into recovery following exercise. RESULTS: Acute HIIE elicited a lower elevation in calprotectin and MPO compared to CME. An increase in MCP-1 was observed across time in both exercise protocols. Furthermore, our analyses did not reveal any significant correlation in percent change (baseline to immediately following exercise) among calprotectin, MCP1, and MPO in neither HIIE nor CME. However, a significant positive correlation was observed in the overall release of calprotectin and MPO across all four time points in both HIIE and CME. Conclusions Our findings indicate that acute HIIE may potentially diminish the systemic release of inflammatory mediators (calprotectin and MPO) compared to CME.