TABLE 6.

Studies investigating the effects of bile acids on depressive-like behavior.

Treatment	Species or strain	Model	Behavioral outcomes	Molecular mechanisms	Reference
FXR knockout mice	C57BL/6 (4-5 months)	-	↓ immobility time in TST but not in FST (improved depressive-like symptoms); ↑ motor activity; impaired memory.	↓ hippocampal GAD65 and ↑ cerebral GAT1; changes in bile acid concentrations in serum (taurodehydrocholic acid, taurocholic acid, deoxycholic acid, glycocholic acid, tauro-α-muricholic acid, tauro-ω-muricholic acid, and hyodeoxycholic acid) and brain (taurocholic acid, taurodehydrocholic acid, tauro-ω-muricholic acid, tauro-β-muricholic acid, deoxycholic acid, and lithocholic acid)	[185]
FXR overexpression (LV-FXR-EGFP)	Male Sprague-Dawley rats (7 weeks)	-	Exacerbates depressive-like behavior in the FST, TST and SPT in naïve rats	No change in hippocampal expression of CREB and CRTC2; ↓ expression of BDNF in hippocampus.	[184]
FXR knockdown (LV-FXR-shRNA-EGFP)	Male Sprague-Dawley rats (7 weeks)	CUMS	Prevents depressive-like behavior in the FST, TST and SPT.	Restores decrease in hippocampal BDNF expression.	[184]
Chronic TUDCA (100, 200 mg/kg; ip) or fluoxetine (20 mg/kg; ip) or TUDCA + fluoxetine co-treatment for 10 days	Male C57BL/6J mice (8-10 weeks)	CUS	TUDCA (at 200 mg/kg) ↓ immobile time in TS and FST; ↑ crossing numbers in the OFT; ↑ sucrose intake in SPT compared to vehicle	TUDCA (at 200 mg/kg) ↓ TNFα and IL-6 in hippocampus and PFC	[192]

BDNF: Brain-Derived Neurotrophic Factor; CREB: Camp Response Element-Binding Protein; CRTC2: CREB-Regulated Transcription Coactivator 2; CUMS: Chronic Unpredictable Mild Stress; CUS: Chronic Unpredictable Stress; FST: Forced-Swim Test; FXR: Farnesoid X Receptor; GAD65: Glutamic Acid Decarboxylase 65; GAT1: GABA Transporter 1; IL-6: Interleukin-6; OFT: Open Field Test; SPT: Sucrose Preference Test; Tnfα: Tumor Necrosis Factor Alpha; TST: Tail Suspension Test; TUDCA: Tauroursodeoxycholic Acid.