The widespread use and pseudo-persistent occurrence of the antidepressant citalopram (CIT) could pose a potential ecological risk in the aquatic environment. The message about the bioconcentration and sensitive biomarker identification of CIT at the environmentally relevant concentrations is limited. In this study, an integral evaluation of the phenotypic and biochemical effects of CIT on Daphnia magna (D. magna) was conducted at 0.5 and 10 µg/L. The biomarker screening includes energy metabolism, phototactic behavior, feeding dysfunction, and antioxidant stress responses. The carbohydrate, lipid, and protein content was determined using the assay of anthrone with glucose as standard, thiophosphorate-Vaniline with cholesterol as standard, and Coomassie brilliant blue with serum albumin as standard, respectively. The results showed the bioconcentration equilibrium of CIT reached at the exposure duration of 48 h during the uptake process. At the exposure concentrations of 0.5 and 10 µg/L, the bioconcentration factor of CIT was 571.2 and 67.4 L/kg, respectively. Both protein and lipid content significantly increased at 0.5 µg/L with a 1.78-fold elevation in total energy. Comparatively, the lipid content showed a significant increase at 10 µg/L, while the available total energy rose by 1.25-fold relative to the control group. The phototactic behavior of D. magna exposed to 0.5 µg/L CIT was markedly reduced at 48 h relative to control. In contrast, a significant decrease in phototaxis was observed after 6 h and then a significant increase at 12 h with a continuously obvious decline at 10 µg/L. The filtration rates were increased by 32% compared to controls at 0.5 µg/L, while the stimulatory effects disappeared at 10 µg/L. With regarding to the antioxidant enzyme activities, CIT exposure significantly inhibited the catalase activity both at 0.5 and 10 µg/L, while the glutathione S-transferase activity was obviously induced at 0.5 µg/L and inhibited at 10 µg/L. The expression level of 18s gene was significantly decreased at 10 µg/L. Only the gst gene expression level was significantly increased at 0.5 µg/L, while the 18s and cat gene expression level was obviously inhibited and induced at 10 µg/L. Comprehensively, the responses of the phenotypic traits and energy metabolism of D. magna at various environmental concentrations were sensitive for CIT. This study provided basic data for the risk estimation of CIT in the real freshwater environment.

The widespread availability and pseudo-persistence of typical psychiatric pharmaceuticals (PDs) can have serious impacts on aquatic ecosystems and even human health. However, the toxicokinetics of typical PDs and the corresponding enzymatic biomarker responses are unclear. In this study, eight typical PDs [carbamazepine (CBZ), citalopram (CIT), sertraline (SER), venlafaxine (VLF), amitriptyline (AMT), chlorpromazine (CPM), quetiapine (QTP) and clozapine (CLZ)] were selected to study the uptake, depuration and biological effects of PDs in Daphnia magna. The results found that the uptake rates (K_u) were in the sequence of VLF < QTP < CBZ < CLZ < CIT < AMT < SER < CPM, while the depuration rates (K_d) were in the order of CLZ < AMT < CIT < SER < QTP < CBZ < CPM < VLF. Correspondingly, the bioconcentration factors (BCFs) followed on as VLF < QTP < CBZ < CIT < AMT < CLZ < SER < CPM. Both pH-dependent octanol–water partition coefficients (log D_ow) and liposome–water partition coefficients (log D_lip-w) exhibited positive correlations with the log BCF of PDs (p < 0.05), indicating the important roles of ionization degree and biological phospholipid contents on bioconcentration. Superoxide dismutase (SOD) activities were evidently induced in the SER and CPM groups, while ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST) activities were significantly induced only in the CBZ group. Acetylcholinesterase (AChE) activity was obviously induced by CBZ, SER and AMT, with levels 1.73, 1.62 and 2.44 times that of the control group (p < 0.05). The K_u of PDs, oxidative stress and metabolic level of D. magna combine to affect BCF levels together. In conclusion, this study contributes to a better understanding of the toxicokinetics and biochemical responses of PDs in D. magna and potential mechanisms of action, which may allow for a better assessment of their environmental health risks to aquatic ecosystems.