To date the modes of actions of pharmaceuticals in

To date, the modes of actions of pharmaceuticals in humans and mammals are well-known (Fent et al., 2006), whereas knowledge of aquatic organisms, particularly invertebrates, is limited. This is problematic as these contaminants/pollutants have potentially harmful effects on wildlife organisms that have identical and/or similar target molecules as pharmaceuticals are developed to target-specific molecular pathways. Some receptors in lower invertebrates are structurally similar to humans and higher vertebrates, suggesting that the molecular mechanisms of pharmaceuticals in mammals may be functionally similar in lower invertebrates (Fent et al., 2006). Recently, acute and chronic toxicity experiments of these compounds have been conducted in aquatic organisms with the marine bacterium Vibrio fischeri, the water flea Daphnia magna, and the Japanese medaka Oryzias latipes (Kim et al., 2007) as well as the cnidarian Hydra attenuata (Quinn et al., 2009), the microalgae Tetraselmis chuii, and the cladoceran Artemia parthenogenetica (Ferreira et al., 2007). However, the traditional endpoints using mortality and growth inhibition cannot explain the in-depth mode of the actions of these pharmaceuticals. To better understand the molecular mechanisms of the toxicological effects of these compounds as an early signal of their toxicity, combined in vivo and in vitro studies are important (Fent, 2001). However, little information is available on the potential ecotoxicological effects at the molecular level of pharmaceuticals in aquatic organisms. Therefore, uncovering a reliable molecular endpoint with a small aquatic organism would be helpful in obtaining knowledge of the effect of pharmaceuticals. The monogonont rotifer, Brachionus koreanus (B. koreanus) is widely distributed along costal lines, and is an important species in its role as an energy transmitter that acts as a primary producer and secondary consumer in aquatic food webs. Due to several advantages (e.g. small size, short generation Dasatinib Monohydrate at ≈24h, simple structure, genetic homogeneity, high fecundity, and easy maintenance in the laboratory), they are considered to be a model species in aquaculture, ecophysiology, ecotoxicology, and environmental genomics (Snell and Janssen, 1995; Dahms et al., 2011). To date, exploration of invertebrate nervous systems were focusing on model animals with diverse experimental approaches but little attention was given as yet on the Rotifera. This happened even though it was shown that rotifers have a primitive brain, located above the mastax, and a neural system throughout the whole body (Kotikova et al., 2005; Hochberg, 2009). Swimming speed alteration by neurotoxic chemicals (e.g. pentachlorophenol, γ-hexachlorocyclohexane, and eserine) revealed a disruption of the neural function in rotifers (Charoy and Janssen, 1999; Garaventa et al., 2010). Previously, Pineda-Rosas et al. (2005) showed acetylcholinesterase (AChE) receptors in six freshwater rotifers, suggesting that rotifer nervous system would be capable to transmit acetylcholine for further signal transduction. However, gene information or protein-relevant data on neurotoxicity were not identified in the Rotifera as yet. As one of molecular endpoints of pharmaceuticals, AChE is a good candidate that is responsible for the hydrolysis of the neurotransmitter acetylcholine (Fukuto, 1990). This enzyme plays a key role in the nervous system and is found mainly in the brain. Inhibition of AChE disrupts the nervous system as accumulating the neurotransmitter, resulting in deleterious effects including death (Koelle, 1994). Thus, AChE activity has been used as a biomarker for environmental pollution, particularly pesticide in aquatic environments. To date, inhibition of AChE activity has been reported in aquatic organisms exposed to methanol (Rico et al., 2006), heavy metals (Banni et al., 2005; Richetti et al., 2011), and pesticides (Anquiano et al., 2009; Ezemonye and Ikpesu, 2011). More recent studies have also showed that some pharmaceuticals increased the inhibition of AChE activity in aquatic organisms (Solé et al., 2010; Li et al., 2012).