5-hydroxytryptamine transporter (5-HTT; SERT) inhibition leading to population decline

Kellie Fay

Anti-depressants such as fluoxetine and sertraline inhibit the reuptake of 5-hydroxytryptamine (5-HT; serotonin)  by blocking the 5-HT transporter (5-HTT), causing an increase in serotonin levels at neural junctions. In molluscs, serotonergic neurons are responsible for the termination of the catch state of muscle contraction (Muneoka and Twarog, 1983). During catch, muscles contract and are resistant to stretch well after excitation by acetylcholine has stopped and intracellular Ca2+ stores return to normal. Importantly, this prolonged contraction is accomplished with minimal (or no) use of energy. While additional phyla may also be able to undergo catch contraction, the role of serotonin in releasing the contraction state appears to be unique to mollusks (Muneoka and Twarog, 1983). In bivalves, catch is used to maintain valve (shell) closure and the presence of serotonin promotes the transition from the passive state to active valve movement; exposure to 5-HTT inhibitors has been observed to cause increased valve movement in swan mussels (Cunha and Machado, 2001). Increased valve movement not only depletes the organism’s energy reserves,but can cause excess water retention in the foot. This water retention is speculated to cause the foot detachment observed in mussels exposed to 5-HTT inhibitors (Cunha and Machado, 2001), although terrestrial gastropods also experience foot detachement (Pavlova 2001). Mussels in the unattached state expend greater energy [54] and are more susceptibility to predation than those attached to a substrate and clumped together (Casey and Chattopadhyay, 2008).

Serotonin has also been identified as a primary neurotransmitter used to control both ciliary and pedal foot locomotion in land and aquatic mollusks (Muneoka et al 1983, Pavlova 2001 , Gosselin 1961, Longley 2010). The specific impacts on locomotion, as well as the concentration-dependence, varies among molluscs because of differing physiology and life history strategies (Fong, 2014). In various bivalves, movement alterations may take the form of increased valve movement, locomotion and mantle display, and/or increased burrowing or burrowing (inappropriately) during daylight hours. The untimely and excessive movement of molluscs due to amplified serotonergic activity could feasibly enhance their visibility and/or diminish their energy reserves, making them more susceptible to predation. Recently, prolonged, low-dose (30-300 ng/L) exposures of mussels to fluoxetine were reported to cause decreases in filter feeding rates, energy reserves and growth (Peters 2016). Foot detachment mentioned above has also been attributed to disrupted coordination of pedal muscle cells and ciliated epithelium of the foot (Pavlova 2001).

This putative AOP should be considered preliminary only.