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ETHNOPHARAMCOLOGICAL RELEVANCE The age-long folkloric use of Uvaria chamae roots in the management of nipple discharge that is not related to pregnancy, childbirth or nursing but as a result of excessive production of prolactin (hyperprolactinemia) is yet to be substantiated with scientific data. AIM OF THE STUDY This study investigated the anti-hyperprolactinemic activities of aqueous extract of Uvaria chamae roots (AEUCR) and associated biochemical changes in chlorpromazine (CPZ)-induced hyperprolactinemic female Wistar rats. MATERIALS AND METHODS A total of sixty female rats (207.40 ± 2.69 g) were assigned into 6 groups. Animals in Group A received 0.5 ml of distilled water only whilst the 7 days CPZ-treated female rats (to induce hyperprolactinemia) in groups B, C, D, E, and F also received distilled water, 2.5 mg/kg body weight of bromocriptine (reference drug), 0.71, 1.41 2.83 mg/kg body weight of AEUCR for 28 days. RESULTS AEUCR contained a total of 15 (75%) amino acids with seven (46.67%) being essential amino acids and eight (53.33%) as non-essential amino acids. Administration of CPZ increased (p<0.05) the levels of prolactin and testosterone, and reduced (p<0.05) the levels of estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), dopamine, triiodothyronine (T3) and tetraiodothyroxine (T4). Chlorpromazine also increased the levels of serum urea, creatinine, total protein, albumin, globulin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) of the animals. In contrast, AEUCR significantly (p<0.05) reduced the CPZ-induced increases in the levels of prolactin and testosterone, and increased the levels of CPZ-induced reduction in the progesterone, estradiol, FSH, LH, dopamine, T3, T4. The AEUCR also reversed (p<0.05) the CPZ-induced related increases in the levels of urea, creatinine, total protein, albumin, globulin, bilirubin, ALT, AST and ALP similar to the trends in the distilled water- and bromocriptine-treated controls. The CPZ-induced remarkable increase in the size of lactating alveolus and lactiferous duct distribution in the mammary gland were restored to normal tubule-alveolar female pattern mammary glands, composed of branching ducts and small alveoli budding off the ducts. CONCLUSION The study concluded that aqueous extract of Uvaria chamae root exhibited anti-hyperprolactinemic activity by restoring prolactin and dopamine levels and tubule-alveolar female pattern in female rats. It also ameliorated CPZ-induced changes in the liver and kidney function indices. This study justifies the folkloric use of Uvaria chamae root in the management of abnormal discharge by the nipples that is unrelated to pregnancy, childbirth and nursing.