GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

Toxicol Appl Pharmacol. 2010 Feb 15;243(1):77-86. doi: 10.1016/j.taap.2009.11.015. Epub 2009 Nov 17.

Abstract

At date the major neuroreceptors i.e. gamma-aminobutyric acid(A) (GABA(A)R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA(A)R agonist (muscimol, MUS; 0.1 microg/g body weight) and/or its antagonist bicuculline (BIC; 1 microg/g body weight) have corroborated a GABA(A)ergic role on motor behaviors. In particular, MUS induced moderate (p<0.05) and great (p<0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatment sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p<0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA(A)R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS+BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA(A)R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

MeSH terms

  • Animals
  • Bicuculline / toxicity*
  • Brain / drug effects
  • Brain / pathology
  • Feeding Behavior / drug effects*
  • Female
  • Fish Diseases / chemically induced
  • Fish Diseases / pathology
  • Male
  • Motor Activity / physiology
  • Muscimol / toxicity*
  • Neurodegenerative Diseases / chemically induced
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / veterinary*
  • Orexin Receptors
  • Perciformes
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, GABA / physiology*
  • Receptors, Neuropeptide / metabolism*
  • Swimming / physiology*

Substances

  • Orexin Receptors
  • Receptors, G-Protein-Coupled
  • Receptors, GABA
  • Receptors, Neuropeptide
  • Muscimol
  • Bicuculline