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Rewarding and aversive doses of caffeine alter activity but not conditioned place preference induced by ethanol in DBA/2J mice.

ABSTRACT: Increases in the consumption of ethanol and caffeine have been attributed to increased subjective feelings of intoxication and pleasure from the combination. Previous studies have shown that caffeine can be rewarding at low doses and aversive at high doses, although these findings are at times inconsistent between studies using comparable doses. Similarly, studies investigating the rewarding effects of ethanol and caffeine combinations have yielded mixed results. To address this issue, the present experiments were designed to investigate the rewarding effects of caffeine, as well as of caffeine?+?ethanol combinations. Male DBA/2J mice were exposed to an unbiased conditioned place preference (CPP) procedure with various doses of caffeine (1, 3, 10,?30?mg/kg) and ethanol (1, 2?g/kg), as well as various conditioning trial durations (5, 30, 60?min). Caffeine dose-dependently increased locomotor activity during conditioning, and produced a biphasic effect on place conditioning. Specifically, a low dose of caffeine (3?mg/kg) produced place preference, while a high dose (30?mg/kg) produced place aversion. When combined with alcohol, caffeine dose-dependently increased ethanol's stimulatory effect. However, the addition of caffeine had no effect on ethanol place preference, as there were no differences in the strength of place preference between mice conditioned with ethanol alone, and mice conditioned with any combination of ethanol and caffeine. These studies add evidence for caffeine's biphasic effects while also emphasizing the importance of considering temporal and methodological parameters when using Pavlovian conditioning procedures to study drug combinations.

SUBMITTER: Zuniga A

PROVIDER: S-EPMC6927548 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Rewarding and aversive doses of caffeine alter activity but not conditioned place preference induced by ethanol in DBA/2J mice.

Zuniga Alfredo A Cunningham Christopher L CL

Pharmacology, biochemistry, and behavior 20191031

Increases in the consumption of ethanol and caffeine have been attributed to increased subjective feelings of intoxication and pleasure from the combination. Previous studies have shown that caffeine can be rewarding at low doses and aversive at high doses, although these findings are at times inconsistent between studies using comparable doses. Similarly, studies investigating the rewarding effects of ethanol and caffeine combinations have yielded mixed results. To address this issue, the prese ...[more]

PMID: 31678181

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Project description: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 ?7 and ?6 but not ?4 and ?2 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.

Dataset Information

Rewarding and aversive doses of caffeine alter activity but not conditioned place preference induced by ethanol in DBA/2J mice.

Publications

Rewarding and aversive doses of caffeine alter activity but not conditioned place preference induced by ethanol in DBA/2J mice.

Similar Datasets

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