The cytisine derivatives, CC4 and CC26, reduce nicotine-induced conditioned place preference in zebrafish by acting on heteromeric neuronal nicotinic acetylcholine receptors
Articolo
Data di Pubblicazione:
2014
Citazione:
The cytisine derivatives, CC4 and CC26, reduce nicotine-induced conditioned place preference in zebrafish by acting on heteromeric neuronal nicotinic acetylcholine receptors / L. Ponzoni, D. Braida, L. Pucci, A. Donzelli, F. Fasoli, I. Manfredi, R.L. Papke, C. Stokes, G. Cannazza, F. Clementi, C. Gotti, M. Sala. - In: PSYCHOPHARMACOLOGY. - ISSN 0033-3158. - 231:24(2014 Dec), pp. 4681-4693. [10.1007/s00213-014-3619-x]
Abstract:
Rationale: Cigarette smoking is one of the most serious health
problems worldwide and people trying to stop smoking have
high rates of relapse. Zebrafish (Danio rerio), by combining
pharmacological and behavioral assays, is a promising animal
model for rapidly screening new compounds to induce
smoking cessation.
Objectives: This study aims to identify possible acetylcholine
nicotinic receptors (nAChRs) involved in mediating nicotine
(NIC)-induced conditioned place preference (CPP) in zebrafishand investigate the effect of the CC4 and CC26 cytisine derivatives in reducing NIC-induced CPP.
Methods: CPP was evaluated using a two-compartment chamber, and the zebrafish were given CC4 (0.001–5 mg/kg), CC26 (0.001–1 mg/kg), cytisine (0.1–2.5 mg/kg), and varenicline (1–10 mg/kg) alone or with NIC (0.001 mg/kg).
Swimming activity was evaluated using a square observational chamber. The affinity of the nicotinic ligands for nativezebrafish brain nAChRs was evaluated by binding studies using [3H]-Epibatidine (Epi) and [125I]-αBungarotoxin (αBgtx) radioligands, and their subtype specificity was determined by means of electrophysiological assay of oocyteexpressed α4β2 and α7 subtypes.
Results: CC4 and CC26 induced CPP with an inverted Ushaped dose–response curve similar to that of NIC.However, when co-administered with NIC, they blocked its reinforcing or slightly aversive effect. Binding and electrophysiological
studies showed that this effect was due to binding to high-affinity heteromeric but not α7-containing receptors.
Conclusions: We have further characterized CC4 and identified a new compound (CC26) that may be active in inducing smoking cessation. Zebrafish is a very useful model for screening new compounds that can affect the rewarding properties
of NIC.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
cytisine derivative ; zebrafish ; conditioned place preference ; nicotine
Elenco autori:
L. Ponzoni, D. Braida, L. Pucci, A. Donzelli, F. Fasoli, I. Manfredi, R.L. Papke, C. Stokes, G. Cannazza, F. Clementi, C. Gotti, M. Sala
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