Sensitization-dependent nicotine place preference in the adult zebrafish

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 92; pp. 457 - 469
• Main Authors: Pisera-Fuster, A., Rocco, L., Faillace, M.P., Bernabeu, R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 08.06.2019
• Subjects: Cocaine; Conditioned place preference; Dopamine neuron markers; Nicotine; Nicotinic acetylcholine receptors; Sensitization; Zebrafish; Conditioned place preference; Nicotinic acetylcholine receptors; Zebrafish; Cocaine; Sensitization; Dopamine neuron markers; Nicotine
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2019.02.018

Sensitization of motor activity is a behavioural test to evaluate the effects of psychostimulants. Conditioned place preference (CPP) is an associative learning procedure to examine the rewarding properties of drugs. We aimed to assess whether motor sensitization to drugs of abuse can make zebrafish more vulnerable to establishing drug-induced CPP. We first evaluated sensitization of locomotor activity of zebrafish to repeated administrations of nicotine and cocaine during 5 days and after 5 days of withdrawal. After withdrawal, when zebrafish were re-exposed to the same dose of nicotine or cocaine locomotor activity was increased by 103% and 166%, respectively. Different groups of zebrafish were sensitized to nicotine or cocaine and trained on a nicotine-CPP task the day after withdrawal. The nicotine dose selected for sensitization was not effective for developing CPP in naïve zebrafish whereas it elicited CPP in zebrafish that were previously sensitized to nicotine or cocaine. Levels of nicotinic acetylcholine receptor β2, α6 and α7 subunit, Pitx3, and tyrosine hydroxylase 1 (TH1) mRNAs were increased in the brain of nicotine- and cocaine-sensitized zebrafish. Nicotine-CPP performed with drug-sensitized zebrafish provoked further enhancements in the expression of α6 and α7 subunit, Pitx3, and TH1 mRNAs suggesting that the expression of these molecules in the reward pathway is involved in both processes. Our findings indicate that repeated exposures to low doses of drugs of abuse can increase subject's sensitivity to the rewarding properties of the same or different drugs. This further suggests that casual drug intake increases the probability of becoming addict. •Nicotine and cocaine induce locomotor sensitization in zebrafish.•Nicotine- and cocaine-sensitized zebrafish showed conditioned place preference to sub-threshold doses of nicotine.•Repeated exposures to low doses of drugs of abuse can increase subjects' sensitivity to the rewarding properties of nicotine.