Unpredictable Chronic Mild Stress Upregulates Dopamine Receptor Expression Independent of Fatty Acid-Binding Protein...

Fatty acid-binding protein 7 (FABP7) assists in the intracellular trafficking of endogenous cannabinoids and polyunsaturated fatty acids (PUFAs) and has been implicated for various psychiatric diseases. Rising evidence demonstrates the crosstalk between the endocannabinoid and dopaminergic systems, particularly in response to stress. The present study seeks to examine the role of FABP7 expression under chronic stress conditions and its impact on the dopaminergic system, specifically dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R) levels. Adult male FABP7^+/+ and FABP7^-/- mice underwent 28-day treatment of unpredictable chronic mild stress (UCMS) procedure. After the stress paradigm, D1R and D2R levels were measured with in vitro autoradiography using [³H] SCH23390 and [³H] Spiperone, respectively. Stressed mice, regardless of genotype, exhibited an increase in D1R binding across the entire striatum (dorsal caudate putamen (CPu), dorsolateral CPu, dorsomedial CPu, ventral CPu, ventrolateral CPu, ventromedial CPu, nucleus accumbens core and shell), substantia nigra and olfactory tract. Additionally, an increase in D2R binding induced by UCMS was observed in the olfactory tract and certain regions of the striatum (dorsal CPu and ventral CPu). The UCMS paradigm upregulates D1R and D2R binding independent of FABP7 gene deletion, suggesting a compensatory role of other FABPs in the brain in maintaining dopaminergic homeostasis. This stress-induced shift in D1R: D2R ratio may underlie the pathogenesis of major depressive disorder and substance use disorder, as well as the high comorbidity among these conditions.