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

Abstract

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.

Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3-M cells by competitively binding to oncogenic FABP5

“…BMS309403 [ 14 – 17 ]. Recently developed FABP5 inhibitors, approximately 50% inhibitory effect of BMS309403, were originally used effectively as analgesic and anti-inflammatory agents in mice [ 18 – 20 ]. These included SBFI26 (α-truxillic acid 1-naphthyl mono-ester).…”

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

“…Cocaine conditioned place preference (CPP) was performed using commercially available equipment (Coulbourn Instruments, Allentown, PA) as pre-viously described (Thanos et al, 2016). Briefly, animals were subjected to one day of a 15 min preconditioning session to evaluate any baseline pref-erence for one of the two CPP test chambers before undergoing conditioning.…”

Indirect and Direct Cannabinoid Agonists Differentially Affect Mesolimbic Dopamine Release and Related Behaviors

“…Previous research has shown that Wistar rats, Sprague-Dawley rats, and B6 mice in standard housing conditions do not have a CPP for AM404, AM404 except at 10.0 mg/kg, or SBFI26 (an inhibitor of FABP5 and FABP7) respectively [98][99][100]. Direct CB1R agonist administration can produce CPP, no preference, or CPA in a drug and dose-dependent manner where THC typically causes a CPP under 5.0 mg/kg and a CPA at 5.0 mg/kg or higher but WIN55,212-2 has variable results where a CPP occurred under 1.0 mg/kg, no preference occurred from 1.0 mg/kg to 3.0 mg/kg, and a CPA occurred from 0.25 mg/kg to 2.5 mg/kg [101,102].…”