Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals.
Prog Neuropsychopharmacol Biol Psychiatry
; 111: 110334, 2021 12 20.
Article
em En
| MEDLINE
| ID: mdl-33905756
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 1â¯mg/L nicotine for 2â¯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 2-60â¯days spontaneous withdrawal. Gene expression analysis using whole brain samples from nicotine-treated and control fish was performed at 7 and 60â¯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 2â¯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 Behavioural differences were associated with brain gene expression changes nicotine withdrawn animals showed decreased expression of chrna 4 and chrna7 after 60â¯days, and of htr2a from 7 to 60â¯days.The expression of c-Fos was significantly increased at 7â¯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 60â¯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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência a Substâncias
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Tabagismo
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Peixe-Zebra
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Emoções
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Mamíferos
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article