Fatty acid binding protein deletion prevents stress-induced preference for cocaine and dampens stress-induced corticosterone levels.

Genetic and pharmacological manipulation of endocannabinoid (eCB) signaling has previously been shown to have an important role on the rewarding properties of drugs of abuse, including cocaine. Recently, fatty acid binding proteins (FABPs) have been proposed as intracellular transporters of the endocannabinoid anandamide (AEA) as well as other bioactive lipids to their catabolic enzyme, fatty acid amide hydrolase (FAAH). The role of these transporters in modulating the brains reward system has yet to be investigated. This study examined the effects of genetic deletion of FABP 5/7 on cocaine preference, as assessed by the Conditioned Place Preference (CPP) paradigm. Male and female wild type (WT) and FABP 5/7 KO mice showed similar acquisition of cocaine CPP, with no differences found in overall locomotor activity. In addition, while male and female WT mice showed stress-induced CPP for cocaine, male and female FABP 5/7 KO mice failed to show a stress-induced preference for the cocaine-paired chamber. Additionally, serum corticosterone levels were analyzed to explore any potential differences in stress response that may be responsible for the lack of stress-induced preference for cocaine. Serum samples were obtained in animals under basal conditions as well as following a 30-min tube restraint stress. Male and female FABP 5/7 KO mice showed reduced corticosterone levels under stress compared to their WT counterparts. The reduction in corticosterone response under stress may mediate that lack of a stress-induced preference for cocaine in the FABP 5/7 KO mice. Thus, the role of FABPs may play an important role in drug-seeking behavior under stressful conditions.

Fatty acid-binding proteins 5 and 7 gene deletion increases sucrose consumption and diminishes forced swim immobility time.

Inhibition and genetic deletion of fatty acid-binding proteins (FABPs) 5 and 7 have been shown to increase the levels of the endocannabinoid anandamide as well as the related N-acylethanolamine's palmitoylethanolamide and oleoylethanolamide. This study examined the role of these FABPs on forced-swim (FS) behavior and on sucrose consumption in two experiments: (experiment 1) using wild-type (WT) mice treated with the FABP inhibitor SBFI26 or vehicle and (experiment 2) using WT and FABP5/7 deficient mice. Results from experiment 1 showed that acute treatment with SBFI26 did not have any effect on sucrose intake or FS behavior in mice. In experiment 2, male and female FABP5/7 deficient mice showed significant increases in sucrose consumption (25 and 21%, respectively) compared with their WT counterparts. In addition, immobility time during the FS was decreased by 27% in both male and female FABP5/7 knockout mice compared with their WT counterparts. The fact that such differences were seen between the acute pharmacological approach and the genetic approach (gene deletion) of FABP needs to be further investigated. The function of FABPs and their specific effects on endocannabinoid anandamide, oleoylethanolamide, and palmitoylethanolamide may play an important role in the development of reward and mood behaviors and could provide opportunities for potential therapeutic targets.

Examination of the Addictive and Behavioral Properties of Fatty Acid-Binding Protein Inhibitor SBFI26.

The therapeutic properties of cannabinoids have been well demonstrated but are overshadowed by such adverse effects as cognitive and motor dysfunction, as well as their potential for addiction. Recent research on the natural lipid ligands of cannabinoid receptors, also known as endocannabinoids, has shed light on the mechanisms of intracellular transport of the endocannabinoid anandamide by fatty acid-binding proteins (FABPs) and subsequent catabolism by fatty acid amide hydrolase. These findings facilitated the recent development of SBFI26, a pharmacological inhibitor of epidermal- and brain-specific FABP5 and FABP7, which effectively increases anandamide signaling. The goal of this study was to examine this compound for any possible rewarding and addictive properties as well as effects on locomotor activity, working/recognition memory, and propensity for sociability and preference for social novelty (SN) given its recently reported anti-inflammatory and analgesic properties. Male C57BL mice were split into four treatment groups and conditioned with 5.0, 20.0, 40.0 mg/kg SBFI26, or vehicle during a conditioned place preference (CPP) paradigm. Following CPP, mice underwent a battery of behavioral tests [open field, novel object recognition (NOR), social interaction (SI), and SN] paired with acute SBFI26 administration. Results showed that SBFI26 did not produce CPP or conditioned place aversion regardless of dose and did not induce any differences in locomotor and exploratory activity during CPP- or SBFI26-paired open field activity. We also observed no differences between treatment groups in NOR, SI, and SN. In conclusion, as SBFI26 was shown previously by our group to have significant analgesic and anti-inflammatory properties, here we show that it does not pose a risk of dependence or motor and cognitive impairment under the conditions tested.