| Summary: | Emerging evidence indicates that the endogenous cannabinoid system modulates the behavioral and physiological effects of nicotine. Fatty acid-binding proteins (FABPs) are among the primary intracellular trafficking mechanisms of endogenous cannabinoids, such as anandamide. To this end, changes in FABP expression may similarly impact the behavioral manifestations associated with nicotine, particularly its addictive properties. <i>FABP5<sup>+/+</sup></i> and <i>FABP5<sup>−/−</sup></i> mice were tested for nicotine-conditioned place preference (CPP) at two different doses (0.1 or 0.5 mg/kg). The nicotine-paired chamber was assigned as their least preferred chamber during preconditioning. Following 8 days of conditioning, the mice were injected with either nicotine or saline. The mice were allowed to access to all the chambers on the test day, and their times spent in the drug chamber on the preconditioning versus the test days were used to examine the drug preference score. The CPP results showed that the <i>FABP5<sup>−/−</sup></i> mice displayed a higher place preference for 0.1 mg/kg nicotine than the <i>FABP5<sup>+/+</sup></i> mice, while no CPP difference was observed for 0.5 mg/kg nicotine between the genotypes. In conclusion, <i>FABP5</i> plays an important role in regulating nicotine place preference. Further research is warranted to identify the precise mechanisms. The results suggest that dysregulated cannabinoid signaling may impact nicotine-seeking behavior.
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