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Behavioral and molecular analysis of nicotine-conditioned place preference in zebrafish.

Kedikian X, Faillace MP, Bernabeu R - PLoS ONE (2013)

Bottom Line: A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment.The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine.Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

ABSTRACT
Studies using mice and rats have demonstrated that nicotine induces a conditioned place preference (CPP), with more effective results obtained by using biased procedures. Zebrafish have also been used as a model system to identify factors influencing nicotine-associated reward by using an unbiased design. Here, we report that zebrafish exhibited putative nicotine biased CPP to an initially aversive compartment (nicotine-paired group). A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment. Zebrafish preference was corroborated by behavioral analysis of several indicators of drug preference, such as time spent in the drug-paired side, number of entries to the drug-paired side, and distance traveled. These results provided strong evidence that zebrafish may actually develop a preference for nicotine, although the drug was administrated in an aversive place for the fish, which was further supported by molecular studies. Reverse transcription-quantitative real-time PCR analysis depicted a significant increase in the expression of α7 and α6 but not α4 and β2 subunits of the nicotinic receptor in nicotine-paired zebrafish brains. In contrast, zebrafish brains from the counterbalanced nicotine group showed no significant changes. Moreover, CREB phosphorylation, an indicator of neural activity, accompanied the acquisition of nicotine-CPP. Our studies offered an incremental value to the drug addiction field, because they further describe behavioral features of CPP to nicotine in zebrafish. The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine. Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates.

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Behavioral effects of nicotine (15 mg/L) on zebrafish in the CPP tank.Analysis of behavioral parameters was performed before and after nicotine conditioning on a 5 min test. Figures a) and b) show the number and duration of motionless positions in the brown side. Figure c) the total distance swum and d) the average velocity, which were calculated by using Ethovision XT7. Data are presented as mean ± SEM. Saline control n = 15, counterbalanced control n = 12, and nicotine-paired n = 21. *p<0.05 and **p<0.01 between pretest and test and #p<0.05 and ##p<0.01 between controls and nicotine-paired group. Control: saline; Nic-unpaired: counterbalanced nicotine treatment and Nic-paired: nicotine treatment associated to the white compartment.
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pone-0069453-g005: Behavioral effects of nicotine (15 mg/L) on zebrafish in the CPP tank.Analysis of behavioral parameters was performed before and after nicotine conditioning on a 5 min test. Figures a) and b) show the number and duration of motionless positions in the brown side. Figure c) the total distance swum and d) the average velocity, which were calculated by using Ethovision XT7. Data are presented as mean ± SEM. Saline control n = 15, counterbalanced control n = 12, and nicotine-paired n = 21. *p<0.05 and **p<0.01 between pretest and test and #p<0.05 and ##p<0.01 between controls and nicotine-paired group. Control: saline; Nic-unpaired: counterbalanced nicotine treatment and Nic-paired: nicotine treatment associated to the white compartment.

Mentions: Figures 5a and b show the number and duration of motionless positions. Significant differences in the number (F2,44 = 6.752; p<0.05) and duration (F2,44 = 8.852; p<0.01) of motionless positions were observed among groups. The number of immobile states was significantly increased (p<0.05) during the test session in control animals (figure 5a). Moreover, we found a significant increase in motionless position duration in control zebrafish in the test compared with the pretest session (p<0.05). The saline control showed significant differences (p<0.05) compared to nicotine-paired but not to nicotine-unpaired group during the test session. It is important to mention that no motionless positions were observed in the white compartment.


Behavioral and molecular analysis of nicotine-conditioned place preference in zebrafish.

Kedikian X, Faillace MP, Bernabeu R - PLoS ONE (2013)

Behavioral effects of nicotine (15 mg/L) on zebrafish in the CPP tank.Analysis of behavioral parameters was performed before and after nicotine conditioning on a 5 min test. Figures a) and b) show the number and duration of motionless positions in the brown side. Figure c) the total distance swum and d) the average velocity, which were calculated by using Ethovision XT7. Data are presented as mean ± SEM. Saline control n = 15, counterbalanced control n = 12, and nicotine-paired n = 21. *p<0.05 and **p<0.01 between pretest and test and #p<0.05 and ##p<0.01 between controls and nicotine-paired group. Control: saline; Nic-unpaired: counterbalanced nicotine treatment and Nic-paired: nicotine treatment associated to the white compartment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722213&req=5

pone-0069453-g005: Behavioral effects of nicotine (15 mg/L) on zebrafish in the CPP tank.Analysis of behavioral parameters was performed before and after nicotine conditioning on a 5 min test. Figures a) and b) show the number and duration of motionless positions in the brown side. Figure c) the total distance swum and d) the average velocity, which were calculated by using Ethovision XT7. Data are presented as mean ± SEM. Saline control n = 15, counterbalanced control n = 12, and nicotine-paired n = 21. *p<0.05 and **p<0.01 between pretest and test and #p<0.05 and ##p<0.01 between controls and nicotine-paired group. Control: saline; Nic-unpaired: counterbalanced nicotine treatment and Nic-paired: nicotine treatment associated to the white compartment.
Mentions: Figures 5a and b show the number and duration of motionless positions. Significant differences in the number (F2,44 = 6.752; p<0.05) and duration (F2,44 = 8.852; p<0.01) of motionless positions were observed among groups. The number of immobile states was significantly increased (p<0.05) during the test session in control animals (figure 5a). Moreover, we found a significant increase in motionless position duration in control zebrafish in the test compared with the pretest session (p<0.05). The saline control showed significant differences (p<0.05) compared to nicotine-paired but not to nicotine-unpaired group during the test session. It is important to mention that no motionless positions were observed in the white compartment.

Bottom Line: A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment.The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine.Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

ABSTRACT
Studies using mice and rats have demonstrated that nicotine induces a conditioned place preference (CPP), with more effective results obtained by using biased procedures. Zebrafish have also been used as a model system to identify factors influencing nicotine-associated reward by using an unbiased design. Here, we report that zebrafish exhibited putative nicotine biased CPP to an initially aversive compartment (nicotine-paired group). A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment. Zebrafish preference was corroborated by behavioral analysis of several indicators of drug preference, such as time spent in the drug-paired side, number of entries to the drug-paired side, and distance traveled. These results provided strong evidence that zebrafish may actually develop a preference for nicotine, although the drug was administrated in an aversive place for the fish, which was further supported by molecular studies. Reverse transcription-quantitative real-time PCR analysis depicted a significant increase in the expression of α7 and α6 but not α4 and β2 subunits of the nicotinic receptor in nicotine-paired zebrafish brains. In contrast, zebrafish brains from the counterbalanced nicotine group showed no significant changes. Moreover, CREB phosphorylation, an indicator of neural activity, accompanied the acquisition of nicotine-CPP. Our studies offered an incremental value to the drug addiction field, because they further describe behavioral features of CPP to nicotine in zebrafish. The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine. Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates.

Show MeSH
Related in: MedlinePlus