Effect of levodopa/carbidopa on stress response in zebrafish

J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2021 May;207(3):393-399. doi: 10.1007/s00359-021-01479-1. Epub 2021 Mar 27.

Abstract

The dopaminergic system of zebrafish is complex and the numerous pathways and receptors in the central nervous system (CNS) are being extensively studied. A critical factor for the synthesis, activation and release of catecholamines (CAs) is the presence of tyrosine hydroxylase, an enzyme which converts L-tyrosine into levodopa. Levodopa thus is the intermediary in the synthesis of dopamine (DA) and norepinephrine (NE) and promotes its release; therefore, CAs play an important role in the CNS with hormonal functions. Here, we use levodopa/carbidopa to clarify the involvement of the dopaminergic pathway in the stress response in zebrafish submitted to an acute stress challenge. Acute stress was induced by chasing fish with a net for 2 min and assessed by measuring whole-body cortisol levels. Two experiments were carried out, the first with exposure to levodopa/carbidopa and the second with exposure to AMPT and levodopa/carbidopa. Levodopa/carbidopa balances the stress response through its action on the zebrafish hypothalamic-pituitary-adrenal (HPA) axis. Changes in cortisol levels suggest that DA was related to the balance of the stress response and that NE decreased this response. These effects were specific to stress since levodopa/carbidopa did not induce changes in cortisol in non-stressed fish.

Keywords: Cortisol; Dopaminergic system; Hypothalamus–pituitary–adrenal axis; Levodopa; Stress response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects*
  • Adrenal Glands / metabolism
  • Animals
  • Carbidopa / pharmacology*
  • Dopamine / metabolism*
  • Dopamine Agonists / pharmacology*
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Drug Combinations
  • Enzyme Inhibitors / pharmacology
  • Female
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Levodopa / pharmacology*
  • Male
  • Stress, Physiological*
  • Tyrosine 3-Monooxygenase / antagonists & inhibitors
  • Tyrosine 3-Monooxygenase / metabolism
  • Zebrafish / metabolism*
  • Zebrafish Proteins / antagonists & inhibitors
  • Zebrafish Proteins / metabolism
  • alpha-Methyltyrosine / pharmacology

Substances

  • Dopamine Agonists
  • Drug Combinations
  • Enzyme Inhibitors
  • Zebrafish Proteins
  • carbidopa, levodopa drug combination
  • Levodopa
  • alpha-Methyltyrosine
  • Tyrosine 3-Monooxygenase
  • Carbidopa
  • Dopamine
  • Hydrocortisone