PUBLICATION
Behavioral and neurochemical profile of MK-801 adult zebrafish model: Forebrain β2-adrenoceptors contribute to social withdrawal and anxiety-like behavior
- Authors
- Perdikaris, P., Dermon, C.R.
- ID
- ZDB-PUB-211214-48
- Date
- 2021
- Source
- Progress in neuro-psychopharmacology & biological psychiatry 115: 110494 (Journal)
- Registered Authors
- Keywords
- Autism-like phenotype, Catecholaminergic, Dopamine transporter, Metabotropic glutamate 5 receptor (mGluR5), Social withdrawal, β(2)-adrenergic receptors
- MeSH Terms
-
- Animals
- Anxiety*
- Behavior, Animal/drug effects
- Disease Models, Animal
- Dizocilpine Maleate/pharmacology*
- Excitatory Amino Acid Antagonists/pharmacology*
- Male
- Prosencephalon/metabolism*
- Receptor, Metabotropic Glutamate 5/metabolism
- Receptors, Adrenergic, beta-2/metabolism*
- Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
- Social Isolation*
- Stereotyped Behavior/drug effects*
- Zebrafish/metabolism*
- PubMed
- 34896197 Full text @ Prog. Neuropsychopharmacol. Biol. Psychiatry
Citation
Perdikaris, P., Dermon, C.R. (2021) Behavioral and neurochemical profile of MK-801 adult zebrafish model: Forebrain β2-adrenoceptors contribute to social withdrawal and anxiety-like behavior. Progress in neuro-psychopharmacology & biological psychiatry. 115:110494.
Abstract
Deficits in social communication and interaction are core clinical symptoms characterizing multiple neuropsychiatric conditions, including autism spectrum disorder (ASD) and schizophrenia. Interestingly, elevated anxiety levels are a common comorbid psychopathology characterizing individuals with aberrant social behavior. Despite recent progress, the underlying neurobiological mechanisms that link anxiety with social withdrawal remain poorly understood. The present study developed a zebrafish pharmacological model displaying social withdrawal behavior, following a 3-h exposure to 4 μΜ (+)-MK-801, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, for 7 days. Interestingly, MK-801-treated zebrafish displayed elevated anxiety levels along with higher frequency of stereotypical behaviors, rendering this zebrafish model appropriate to unravel a possible link of catecholaminergic and ASD-like phenotypes. MK-801-treated zebrafish showed increased telencephalic protein expression of metabotropic glutamate 5 receptor (mGluR5), dopamine transporter (DAT) and β2-adrenergic receptors (β2-ARs), supporting the presence of excitation/inhibition imbalance along with altered dopaminergic and noradrenergic activity. Interestingly, β2-ARs expression, was differentially regulated across the Social Decision-Making (SDM) network nodes, exhibiting increased levels in ventral telencephalic area (Vv), a key-area integrating reward and social circuits but decreased expression in dorso-medial telencephalic area (Dm) and anterior tuberal nucleus (ATN). Moreover, the co-localization of β2-ARs with elements of GABAergic and glutamatergic systems, as well as with GAP-43, a protein indicating increased brain plasticity potential, support the key-role of β2-ARs in the MK-801 zebrafish social dysfunctions. Our results highlight the importance of the catecholaminergic neurotransmission in the manifestation of ASD-like behavior, representing a site of potential interventions for amelioration of ASD-like symptoms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping