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

Journal Article · Sun Feb 14 23:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.11.015· OSTI ID:21344868

Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello ^[1]

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1. Comparative Neuroanatomy Laboratory, Ecology Department, University of Calabria, 87030 Arcavacata di Rende (Italy)

At date the major neuroreceptors i.e. gamma-aminobutyric acid{sub A} (GABA{sub 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{sub A}R agonist (muscimol, MUS; 0,1 mug/g body weight) and/or its antagonist bicuculline (BIC; 1 mug/g body weight) have corroborated a GABA{sub 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{sub 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{sub A}R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

• OSTI ID: 21344868
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 243; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
BRAIN
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CEREBELLUM
DOSES
DRUGS
ELECTRON MICROSCOPY
ELEMENTS
HOMEOSTASIS
MEMBRANE PROTEINS
MEMBRANES
MESSENGER-RNA
METALS
MICROSCOPY
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RECEPTORS
RNA
SILVER
TRANSITION ELEMENTS
TRANSMISSION ELECTRON MICROSCOPY