Abstract
The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity. However, acute puerarin treatment did not ameliorate the antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore, puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH). Collectively, repeated administration of puerarin alleviated the behavioral deficits induced by chronic stress which was associated with the biosynthesis of neurosteroids, normalization of serotonergic system and preventing HPA axis dysfunction.
Highlights
Major depressive disorder (MDD) is a debilitating and chronic disorder with high probability of medical and psychiatric co-morbidity, functional impairment, as well as significant societal and personal costs1, 2
The results indicated that puerarin ameliorated the chronic unpredictable stress (CUS)-induced behavioral deficits in sucrose preference test (SPT)
We preliminarily evaluate the effects of puerarin on CUS-induced behavioral deficits via the CUS model and its possible mechanism
Summary
Major depressive disorder (MDD) is a debilitating and chronic disorder with high probability of medical and psychiatric co-morbidity, functional impairment, as well as significant societal and personal costs . Long-term use of these drugs induces multiple inevitable side effects, including cognitive dysfunction, sexual dysfunction, dependence, weight gain, sedation and withdrawal . Long-term use of these drugs induces multiple inevitable side effects, including cognitive dysfunction, sexual dysfunction, dependence, weight gain, sedation and withdrawal5, 6 Based on these drawbacks, considerable effort has been invested in search for better drugs for more effective treatments of depressive-like behavior. There has been considerable popular interest in using natural extracts and plant preparations to treat depressive-like disorder. The molecular and cellular mechanisms underlying the antidepressant-like effects of puerarin are remain unclear. Hyperactivity of the HPA axis in stress/depressive-like behavior is thought to be related to reduced feedback inhibition by endogenous hormones of corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH), which are commonly detected hormones in clinical patients and animal models. Evidences from various studies indicated that the levels of monoamine neurotransmitters in the brain were increased after the treatments of antidepressants
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