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Effects of aripiprazole on caffeine-induced hyperlocomotion and neural activation in the striatum

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Abstract

Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. In addition to its antipsychotic activity, this compound blocks the effects of some psychostimulant drugs. It has not been verified, however, if aripiprazole interferes with the effects of caffeine. Hence, this study tested the hypothesis that aripiprazole prevents caffeine-induced hyperlocomotion and investigated the effects of these drugs on neural activity in the striatum. Male Swiss mice received injections of vehicle or antipsychotic drugs followed by vehicle or caffeine. Locomotion was analyzed in a circular arena and c-Fos protein expression was quantified in the dorsolateral, dorsomedial, and ventrolateral striatum, and in the core and shell regions of nucleus accumbens. Aripiprazole (0.1, 1, and 10 mg/kg) prevented caffeine (10 mg/kg)-induced hyperlocomotion at doses that do not change basal locomotion. Haloperidol (0.01, 0.03, and 0.1 mg/kg) also decreased caffeine-induced hyperlocomotion at all doses, although at the two higher doses, this compound reduced basal locomotion. Immunohistochemistry analysis showed that aripiprazole increases c-Fos protein expression in all regions studied, whereas caffeine did not alter c-Fos protein expression. Combined treatment of aripiprazole and caffeine resulted in a decrease in the number of c-Fos positive cells as compared to the group receiving aripiprazole alone. In conclusion, aripiprazole prevents caffeine-induced hyperlocomotion and increases neural activation in the striatum. This latter effect is reduced by subsequent administration of caffeine. These results advance our understanding on the pharmacological profile of aripiprazole.

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Acknowledgments

The authors thank the financial support from FAPEMIG (APQ-01728-13).

FAM is a recipient of a CNPq productivity fellowship (level 2). The authors declare that they have no conflict of interest

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Authors and Affiliations

  1. Graduate School in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Luara A. Batista

  2. Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil

    Thércia G. Viana, Vívian T. Silveira, Daniele C. Aguiar & Fabrício A. Moreira

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  1. Luara A. Batista
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  2. Thércia G. Viana
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  3. Vívian T. Silveira
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  5. Fabrício A. Moreira
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Correspondence to Fabrício A. Moreira.

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Batista, L.A., Viana, T.G., Silveira, V.T. et al. Effects of aripiprazole on caffeine-induced hyperlocomotion and neural activation in the striatum. Naunyn-Schmiedeberg's Arch Pharmacol 389, 11–16 (2016). https://doi.org/10.1007/s00210-015-1170-x

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