Evaluation of drug seeking behavior on nicotine conditioned place preference in zebrafish

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Dec 20:119:110593. doi: 10.1016/j.pnpbp.2022.110593. Epub 2022 Jun 28.


Seeking of drugs is commonly evaluated in a specific environment for assessing drug preference. However, cognitive strategies involved in drug seeking are mostly unknown. To assess the strength of environmental cues that can be associated with nicotine in the zebrafish brain reward circuitry, we have designed herein a modified conditioned place preference (CPP) paradigm. This task was devised to identify salient environmental cues relevant for strong nicotine-environment association and drug seeking induction. During test sessions, background colors of the CPP tank chambers were shifted and preference for colors associated to nicotine was assessed. We have compared several tank designs and different compartment colors. Our findings indicated that zebrafish seeking behavior was strongly dependent on compartment color shades. Combination of red and yellow environments, which were preferred and avoided compartments, respectively, was the most effective design presenting the highest CPP-score. Interestingly, animals that stayed for longer periods in the environment conditioned to nicotine during a first testing interval were also able to follow the background color shade conditioned to nicotine to the other compartment immediately after background colors were relocated between compartments. During a second testing period, zebrafish also stayed for longer periods in the colored compartment paired to nicotine during conditioning. These findings suggest that under salient environmental conditions, zebrafish voluntarily followed a shifting visual cue previously associated with nicotine delivery. Furthermore, our findings indicate that zebrafish exhibit spatial associative learning and memory, which generates a repertoire of conspicuous locomotor behaviors induced by nicotine preference in the CPP task.

Keywords: Background color preference; Conditioned place preference; Nicotine; Seeking behavior; Visual cue relocation; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Classical
  • Drug-Seeking Behavior
  • Nicotine* / pharmacology
  • Reward
  • Zebrafish*


  • Nicotine