Fluoxetine and WAY 100,635 dissociate increases in scototaxis and analgesia induced by conspecific alarm substance in zebrafish (Danio rerio Hamilton 1822)

Abstract

Alarm reactions to a substance secreted by the damaged skin of conspecifics and closely-related species are increasingly being recognized as fear-like responses in fish. The neurochemical underpinnings of these effects are so far unknown; however, given the role of the serotonergic system on defensive behavior, it is possible that the alarm reaction is mediated by this monoamine. Exposure to conspecific alarm substance (CAS) increased anxiety-like behavior in the light/dark test in zebrafish and decreased nocifensive behavior. These effects were accompanied by increases in blood glucose, hemoglobin, epinephrine and norepinephrine levels, as well as extracellular levels of serotonin in the brain. Pretreatment with fluoxetine blocked the anxiogenic effects of CAS on the light/dark test as well as all physiological parameters and the increase in extracellular brain 5-HT, but not the reduction in nocifensive behavior. Conversely, pretreatment with the 5-HT1AR antagonist WAY 100635 blocked the effects on nocifensive behavior, but not the effects on anxiety-like behavior nor on physiological parameters. These results point to an important and complex role of the serotonergic system in the mediation of fear-potentiated behavior in the light/dark test and in fear-induced analgesia in zebrafish.

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

“…When zebrafish are exposed to this alarm substance and subsequently tested in the light/dark test, an increase in defensive behaviour is observed that is blocked by acute pretreatment with fluoxetine (Maximino et al, 2014b). Interestingly, the same fluoxetine dose increases the same behaviour in this test when given to animals that were not exposed to alarm substance (Maximino et al, 2014b), suggesting that this drug is anxiogenic and panicolytic. Alarm substance also increases plasma levels of norepinephrine, epinephrine, and glucose, effects which were blocked by fluoxetine (Maximino et al, 2014b).…”

“…Alarm substance also increases plasma levels of norepinephrine, epinephrine, and glucose, effects which were blocked by fluoxetine (Maximino et al, 2014b). Both behavioural and autonomic effects, however, were not blocked by treatment with WAY 100,635 (Maximino et al, 2014b); interestingly, when animals are exposed to the alarm substance during the novel tank test, WAY 100,635 and methysergide (a 5-HT2 receptor antagonist) potentiate the effect of alarm substance (Nathan et al, 2015).…”

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

“…When zebrafish are exposed to this alarm substance and subsequently tested in the light/dark test, an increase in aversive behaviour is observed that is blocked by acute pretreatment with fluoxetine (Maximino et al, 2014b). Interestingly, the same fluoxetine dose increases the same behaviour in this test when given to animals that were not exposed to alarm substance (Maximino et al, 2014b), suggesting that this drug is anxiogenic and panicolytic. alarm substance also increases plasma levels of norepinephrine, epinephrine, and glucose, effects which were blocked by fluoxetine (Maximino et al, 2014b).…”

“…alarm substance also increases plasma levels of norepinephrine, epinephrine, and glucose, effects which were blocked by fluoxetine (Maximino et al, 2014b). Both behavioural and autonomic effects, however, were not blocked by treatment with WAY 100,635 (Maximino et al, 2014b); interestingly, when animals are exposed to the alarm substance during the novel tank test, WAY 100,635 and methysergide (a 5-HT 2 receptor antagonist) potentiate the effect of alarm substance (Nathan et al, 2015).…”

Sensory Ecology of Ostariophysan Alarm Substances

“…There is now ample evidence that CAS increases vigilance, leading to antipredator 165 behavior such as that described in Box 2, as well as long-term alterations in foraging (Oswald & 166 Robison, 2011), fear-induced analgesia (Maximino, 2011;Maximino et al, 2014), and avoidance of 167 8/37 areas in which CAS is detected (Chivers & Smith, 1994;Wisenden et al, 1995) or which were 168 previously associated with CAS (Ruhl et al, 2017;Maximino et al, 2018). Guppies (Poecilia 169 reticulata) exposed to CAS are more attentive to visual cues (Stephenson, 2016), and zebrafish 170 (Danio rerio) exposed to CAS show increased risk assessment in the light/dark test (Quadros et al,171 2016; but see Maximino et al, 2014), suggesting that CAS increases alertness to threatening cues in 172 other sensory modalities. On the other hand, CAS was not able to increase antipredator responses to 173 a sympatric predator (although the predator was not in the same tank as the receiver) in zebrafish 174 , although CAS increased survival of fathead minnows (Pimephales 175 promelas) placed in an experimental tank with a predator (Mathis & Smith, 1993).…”