PUBLICATION
Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals
- Authors
- Ponzoni, L., Melzi, G., Marabini, L., Martini, A., Petrillo, G., Teh, M.T., Torres-Perez, J.V., Morara, S., Gotti, C., Braida, D., Brennan, C.H., Sala, M.
- ID
- ZDB-PUB-210428-28
- Date
- 2021
- Source
- Progress in neuro-psychopharmacology & biological psychiatry 111: 110334 (Journal)
- Registered Authors
- Brennan, Caroline
- Keywords
- Emotion, Hyperkatifeia, IEG, Memory, Nicotine dependence, TH
- MeSH Terms
-
- Anhedonia/physiology
- Animals
- Anxiety/etiology
- Anxiety/physiopathology
- Brain/physiology
- Emotions/physiology*
- Female
- Gene Expression
- Male
- Mammals*
- Receptors, Nicotinic
- Substance Withdrawal Syndrome*
- Time Factors
- Tobacco Use Disorder*
- Tyrosine 3-Monooxygenase/analysis
- Zebrafish*
- PubMed
- 33905756 Full text @ Prog. Neuropsychopharmacol. Biol. Psychiatry
Citation
Ponzoni, L., Melzi, G., Marabini, L., Martini, A., Petrillo, G., Teh, M.T., Torres-Perez, J.V., Morara, S., Gotti, C., Braida, D., Brennan, C.H., Sala, M. (2021) Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals. Progress in neuro-psychopharmacology & biological psychiatry. 111:110334.
Abstract
Background Nicotine withdrawal syndrome is a major clinical problem. Animal models with sufficient predictive validity to support translation of pre-clinical findings to clinical research are lacking.
Aims We evaluated the behavioural and neurochemical alterations in zebrafish induced by short- and long-term nicotine withdrawal.
Methods Zebrafish were exposed to 1 mg/L nicotine for 2 weeks. Dependence was determined using behavioural analysis following mecamylamine-induced withdrawal, and brain nicotinic receptor binding studies. Separate groups of nicotine-exposed and control fish were assessed for anxiety-like behaviours, anhedonia and memory deficits following 2-60 days spontaneous withdrawal. Gene expression analysis using whole brain samples from nicotine-treated and control fish was performed at 7 and 60 days after the last drug exposure. Tyrosine hydroxylase (TH) immunoreactivity in pretectum was also analysed.
Results Mecamylamine-precipitated withdrawal nicotine-exposed fish showed increased anxiety-like behaviour as evidenced by increased freezing and decreased exploration. 3H-Epibatidine labeled heteromeric nicotinic acethylcholine receptors (nAChR) significantly increased after 2 weeks of nicotine exposure while 125I-αBungarotoxin labeled homomeric nAChR remained unchanged. Spontaneous nicotine withdrawal elicited anxiety-like behaviour (increased bottom dwelling), reduced motivation in terms of no preference for the enriched side in a place preference test starting from Day 7 after withdrawal and a progressive decrease of memory attention (lowering discrimination index). Behavioural differences were associated with brain gene expression changes: nicotine withdrawn animals showed decreased expression of chrna 4 and chrna7 after 60 days, and of htr2a from 7 to 60 days.The expression of c-Fos was significantly increased at 7 days. Finally, Tyrosine hydroxylase (TH) immunoreactivity increased in dorsal parvocellular pretectal nucleus, but not in periventricular nucleus of posterior tuberculum nor in optic tectum, at 60 days after withdrawal.
Conclusions Our findings show that nicotine withdrawal induced anxiety-like behaviour, cognitive alterations, gene expression changes and increase in pretectal TH expression, similar to those observed in humans and rodent models.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping