RESUMEN
Human pharmaceuticals are pollutants of special concern due to their widespread consumption over the last decades, their high persistence in the environment, and the reported alterations produced on non-target organism. The antidepressant fluoxetine (FLX) exerts its effect by inhibiting serotonin (5-HT) reuptake at the presynaptic membrane, thus increasing brain serotonergic activity. In vertebrates, there is a clear inverse relationship between hypothalamic 5-HT levels and food intake, therefore we hypothesized that FLX would inhibit food intake, and in consequence alter energy metabolism in freshwater fish. The aim of this study was to analyze the effect of FLX on feeding behavior and energy storage of the cichlid fish Cichlasoma dimerus. Adult fish were intraperitoneally injected daily with 2 or 20⯵g.g-1 FLX or saline for a 5-day period, during which the 20⯵g.g-1 FLX-injected fish exhibited a marked reduction in food intake, consistent with a decrease in total body weight and total hepatocyte area observed at the end of the experiment. Although not statistically significant, a marked 50% decrease in glycogen and lipid content and an increase in protein levels in liver was observed for the 20⯵g.g-1 FLX dose. This was evidenced histochemically by a weak PAS positive reaction and an intense Coomasie Blue stain. Taken together, these results suggest that the SSRI antidepressant FLX produces an anorectic effect in adults of C. dimerus, which could alter normal physiological function and, in consequence, have a negative impact on fish growth, reproduction, and population success.
Asunto(s)
Cíclidos/metabolismo , Metabolismo Energético/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Fluoxetina/toxicidad , Inhibidores Selectivos de la Recaptación de Serotonina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Hígado/metabolismo , Masculino , Reproducción/efectos de los fármacosRESUMEN
Chemical pollution from pharmaceuticals is increasingly recognized as a major hazard to the aquatic biota. Among the wide variety of pharmaceuticals, fluoxetine (FLX) is one of the most widely prescribed antidepressants, and therefore, it is frequently identified in the aquatic environment. As FLX is designed to alter human behaviour and many physiological pathways are conserved across vertebrates, this drug may affect the behaviour of fish living in FLX-polluted environments. Here, we exposed groups of female mosquitofish Gambusia holbrooki to waterborne FLX for 14 days, under semi-static conditions with daily renewal of test solutions. Following exposure, we conducted a set of behavioural assays in individual fish, aimed at assessing the effects of FLX on their locomotor activity and behavioural responses. We found that FLX impaired swimming behaviour at high concentrations (25⯵g/L and 50⯵g/L) but not at low concentrations close to environmental levels (1⯵g/L and 5⯵g/L). When swimming activity was assessed 5â¯min after transfer of the focal fish to the testing tank, 50⯵g/L FLX was the only concentration showing significant effects. However, when the same trials were performed 24â¯h later, 25⯵g/L FLX turned out to be an effect concentration in addition to 50⯵g/L. Interestingly, these concentrations would elicit fish plasma concentrations comprised within the range of human therapeutic doses. When subjected to a light/dark preference test, fish showed tendency to remain less time in the dark area at high FLX concentrations, thus suggesting an anti-anxiety response. Shoaling behaviour was not affected by FLX exposure. Our study contributes to the growing body of literature evaluating the effects of FLX on animal behaviour. Regarding the experimental design used in behavioural testing, our findings suggest that focal fish should be subjected to long habituation periods, namely of at least a few hours, in order to better assess the effects of drug exposure.
Asunto(s)
Antidepresivos/toxicidad , Conducta Animal/efectos de los fármacos , Ciprinodontiformes/fisiología , Fluoxetina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Femenino , Natación , Pruebas de ToxicidadRESUMEN
Among the wide variety of pharmaceuticals released into the environment, Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is one of the most prescribed for the treatment of major depression. It inhibits serotonin (5-HT) reuptake at the presinaptic membrane, increasing serotonergic activity. In vertebrates, including fish, the serotonergic system is closely related to the Hypothalamic Pituitary Gonadal (HPG) axis which regulates reproduction. As FLX can act as an endocrine disrupting compound (EDC) by affecting several reproductive parameters in fish, the aim of this study was to provide an integral assessment of the potential effect of FLX on the reproductive axis of the Neotropical freshwater fish Cichlasoma dimerus. Adult fish were intraperitoneally injected with 2 µg g-1 FLX or saline every third day for 15 days. No significant differences were found on serotonergic turnover (5-HIAA/5-HT ratio). Pituitary ßLH content in FLX injected females was significantly higher than control females; no significant differences were seen for ßFSH content. Sex steroids remained unaltered, both in males and females fish, after FLX treatment. No plasma vitellogenin was induced in treated males. Some alterations were seen in testes of FLX injected males, such as the presence of foam cells and an acidophilic PAS positive, Alcian-Blue negative secretion in the lobular lumen. Although there is no clear consensus about the effect of this drug on reproductive physiology, these results indicate that FLX is acting as a mild EDC in adults of C. dimerus.