Dopaminergic control of anxiety in young and aged zebrafish

Abstract

Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wildtype (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed. We established that DAT-KO results in a chronic anxiety-like state, seen as an increase in bottom-dwelling and thigmotaxis. Similar effects were produced by aging and acute cocaine administration, both leading to reduction in DAT mRNA abundance (qPCR). Inhibition of D1 activity counteracted the anxiety-like effects associated with DAT deficit, independent of its origin. Inhibition of D2/D3 receptors reduced anxiety in young DAT-KO, enhanced the anxiogenic effects of cocaine in WT, but did not affect aged WT or DAT-KO fish. These findings provide new evidence that the dopaminergic system plays a critical role in anxiety-like states, and suggest that adult zebrafish provide a sensitive diurnal vertebrate model for elucidating the molecular mechanisms of anxiety and a platform for anxiolytic drug screens.

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

“…Treatment with the dopamine transporter blocker D-amphetamine increases defensive behaviour in the novel tank test without apparent locomotor effects (Kyzar et al, 2013). Similarly, the D1 receptor antagonist SCH 23390 decreases defensive behaviour (Kacprzak et al, 2017) and reduces social preference (Scerbina et al, 2012) in zebrafish. A developmental role for catecholamines is also suggested by experiments with morpholino knockdown of the tyrosine hydroxylase-coding gene th1, which decreases defensive behaviour when the animal reaches adulthood (Formella et al, 2012).…”

“…A developmental role for catecholamines is also suggested by experiments with morpholino knockdown of the tyrosine hydroxylase-coding gene th1, which decreases defensive behaviour when the animal reaches adulthood (Formella et al, 2012). Moreover, dopamine transporter-null zebrafish are more sensitive to the D2/D3 receptor antagonist sulpiride (Kacprzak et al, 2017).…”

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

“…A developmental role for catecholamines is also suggested by experiments with morpholino knockdown of the tyrosine hydroxylase-coding gene th1, which decreases anxiety-like behaviour when the animal reaches adulthood (Formella et al, 2012). Moreover, dopamine transporter-null zebrafish are more sensitive to the D 2 /D 3 receptor antagonist sulpiride (Kacprzak et al, 2017).…”

“…Treatment with the dopamine transporter blocker D-amphetamine increases anxiety-like behaviour in the novel tank test without apparent locomotor effects (Kyzar et al, 2013). Similarly, the D 1 receptor antagonist SCH 23390 decreases anxiety-like behaviour (Kacprzak et al, 2017) and reduces social preference (Scerbina et al, 2012) in zebrafish. A developmental role for catecholamines is also suggested by experiments with morpholino knockdown of the tyrosine hydroxylase-coding gene th1, which decreases anxiety-like behaviour when the animal reaches adulthood (Formella et al, 2012).…”

The integration of sociality, monoamines and stress neuroendocrinology in fish models: applications in the neurosciences

“…Treatment with the dopamine transporter blocker d ‐amphetamine increases defensive behaviour in the novel‐tank test without apparent locomotor effects (Kyzar et al ., ). Similarly, the D 1 receptor antagonist SCH 23390 decreases defensive behaviour (Kacprzak et al ., ) and reduces social preference (Scerbina et al ., ) in D. rerio . A developmental role for catecholamines is also suggested by experiments with morpholino knockdown of the tyrosine hydroxylase‐coding gene th1 , which decreases defensive behaviour when the animal reaches adulthood (Formella et al ., ).…”