Diazepam and Fluoxetine Decrease the Stress Response in Zebrafish

Abstract

The presence of pharmaceutical products in the aquatic environment has been reported in several studies. However, the impact of these drugs on living organisms is still uncharacterized. Here, we investigated the effects of acute exposure to either diazepam or fluoxetine on the stress response in Danio rerio. We showed that diazepam and fluoxetine inhibited the stress axis in zebrafish. Intermediate concentrations of diazepam suppressed the stress response as measured by cortisol levels, whereas fluoxetine inhibited cortisol increase at concentrations similar to those found in the environment. These data suggest that the presence of psychoactive drugs in aquatic ecosystems could cause neuroendocrine dysfunction in fish.

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

“…However, peak levels of whole-body cortisol are observed 15 min after stress (de Abreu et al, 2014), an effect that is also blocked by fluoxetine. If stress-induced cortisol responses were causally related to the pro-defensive effect of stress, the temporal order of these effects should be inverted.…”

“…In goldfish (Carassius auratus L.) and Arctic charr (Salvelinus alpinus L.), 5-HT1A and 5-HT4 receptor activation increase cortisol responses by acting directly in steroidogenic cells in the interrenals (Lim et al, 2013). However, these effects appear to be different in stressed animals, as fluoxetine blocks cortisol responses after chasing stress in zebrafish (de Abreu et al, 2014), and the 5-HT1A receptor agonist 8-OH-DPAT does the same in the Arctic charr (Höglund et al, 2002). Höglund et al (2002) There are some methodological issues in mapping behavioural and neuroendocrine roles for 5-HT in stress, as well.…”

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

“…However, peak levels of whole-body cortisol are observed 15 min after stress (de Abreu et al, 2014), an effect that is also blocked by fluoxetine. If stress-induced cortisol responses were causally related to the anxiogenic effect of stress, the temporal order of these effects should be inverted.…”

“…In goldfish and Arctic charr, 5-HT 1A and 5-HT 4 receptor activation increase cortisol responses by acting directly in steroidogenic cells in the interrenals (Lim et al, 2013). However, these effects appear to be different in stressed animals, as fluoxetine blocks cortisol responses after chasing stress in zebrafish (de Abreu et al, 2014), and the 5-HT 1A receptor agonist 8-OH-DPAT does the same in the Arctic charr (Höglund et al, 2002). Höglund et al (2002) observed that fish receiving this drug with a permanent intraperitoneal catheter, thus decreasing the stress of injection, showed increased cortisol and adrenocorticotropic hormone (ACTH) levels, while animals which received (stressful) intraperitoneal injections responded with decreased plasma cortisol and ACTH levels.…”

First evidence that waterborne methylphenidate alters endocrine and behavioral stress responses in zebrafish

“…Zebrafish (Danio rerio) is widely used as a model organism because of its genetic homology to humans and ease of maintenance and handling [8][9][10]. Many ecotoxicology studies have reinforced the use of zebrafish as a model to predict the impact of pharmaceutical waste exposure on aquatic organisms [11][12][13][14][15].…”