Behavioural responses of fish larvae modulated by analgesic drugs after a stress exposure

Where to Draw the Line? Should the Age of Protection for Zebrafish be Lowered?

“…When exposed to potentially painful stimuli, acidic chemicals and hot temperature, the larvae significantly reduce their activity. [10][11][12] This reduction in activity has been observed in adults in a variety of studies after painful treatments. [13][14][15] Administering pain-relieving drugs to both larvae and adults prevented the decrease in activity in these experiments; therefore, the underlying mechanisms involved are likely to be similar between larvae five dpf and adults.…”

Ethical considerations in fish research

“…Indomethacin injected intraperitoneally (20 μl of 0.2 mg ml −1 ) did reduce pain related responses in adult D. rerio treated with formalin (Magalhaes et al ., ). Aspirin administered via immersion prevented the reduced activity seen in adult and larval D. rerio when subjected to noxious events (Lopez‐Luna et al ., ,b,c,d; Schroeder & Sneddon, ). Future studies need to investigate NSAIDs further to determine the minimum effective dose and explore any unwanted side‐effects since long‐term use of these drugs in mammals, birds and reptiles can result in gastric ulcers or renal disease.…”

“…Lidocaine effectively prevents behavioural and physiological alterations in O. mykiss during subcutaneous injection of acetic acid (Mettam et al ., ). Exposure to lidocaine by emersion also ameliorates substantial changes in the behaviour of adult D. rerio subject to caudal‐fin clipping (Schroeder & Sneddon, ; Deakin et al ., ) and was also effective when used with larval D. rerio exposed to noxious chemical and thermal stimuli (Lopez‐Luna et al ., ,b,c,d). Infiltration of rainbow trout with lidocaine appears to damage skeletal muscle and connective tissue with higher concentrations of (10 mg kg −1 ) but not to cause adverse behavioural side‐effects (20 mg kg −1 ), compared with saline infiltration (Chatigny et al ., 2018a,b).…”

“…Empirical studies in fishes have also confirmed the presence of nociceptors, demonstrating their properties are very similar to those found in humans and other mammals (Ashley et al ., , ; Mettam et al ., ; Sneddon, , , ). Studies in fishes have demonstrated changes in brain activity during noxious stimuli (Dunlop & Laming, ; Nordgreen et al ., ; Reilly et al ., ; Sneddon, ) and recorded adverse changes in behaviour and physiology during noxious treatments (Dunlop et al ., ; Maximino, ; Mettam et al ., ; Reilly et al ., ; Roques et al ., ; Sneddon, ; Sneddon et al ., , ; White et al ., ) all of which can be prevented by analgesics known to be effective in relieving pain in mammals (Lopez‐Luna et al ., , , , ; Mettam et al ., ; Newby et al ., ; Nordgreen et al ., ; Schroeder & Sneddon, ; Sneddon, , ; Taylor et al ., ). This empirical evidence taken together supports the idea that fishes may experience pain.…”

“…Opioids inhibit neurotransmitter release pre‐synaptically thereby blocking nociceptors but these drugs also block central transmission. Several studies have shown morphine is an effective analgesic in O. mykiss (Baker et al ., ; Jones et al ., ; Sneddon, ) and other species ( e.g ., goldfish Carassius auratus (L. 1758); Nordgreen et al ., ; D. rerio , Lopez‐Luna et al ., ,b,c,d; Magalhaes et al ., ; Schroeder & Sneddon, ; Taylor et al ., ). Morphine has a pharmocokinetically similar action in fishes compared with mammals, however, morphine persists for a prolonged period after administration due to slower excretion rates (half‐life 37 h; Newby et al ., , ).…”