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Effect of coadministration of the GABAB agonist baclofen and the 5-HT2C agonist Ro60-0175 on the expression of amphetamine-induced locomotor sensitization

  • Laura N. Cedillo
  • Rosa Isela Ruíz-García
  • Juan C. Jiménez
  • Florencio MirandaEmail author
Research Article
  • 12 Downloads

Abstract

GABAB and 5-HT2C agonists are effective in attenuating the behavioral effects of psychostimulants. However, they induce adverse side effects when used in high doses. The previous evidence has suggested that the 5HT2C receptor activation effect could be produced by an increased release of GABA in the ventral tegmental area (VTA) and the consequent activation of GABAergic receptors. Therefore, the objective of this study was to evaluate the effects of joint administration of an intermediate dose of the GABAB agonist baclofen (3.0 mg/kg) with different doses of the 5HT2C agonist Ro60-0175 (0.3, 1.0, and 3.0 mg/kg) on the locomotor sensitization expression induced by the repeated administration of amphetamine (1.0 mg/kg). Our results showed an attenuation of the expression of sensitization in a dose-dependent manner with both agonists. In both cases, we observed a complete blockade at the highest dose. In addition, the intermediate dose of baclofen increased the effects of the three doses of Ro60-0175. These results support the role of the joint action of GABAB and 5-HT2C receptors in the effects of psychostimulants. However, it remains to be explored whether the observed effect can be attributed to receptors located in the VTA or the nucleus accumbens.

Keywords

Amphetamine Locomotor sensitization Baclofen 

Notes

Acknowledgements

This study was supported by grant IN301717 from PAPIIT-UNAM (Mexico).

Author contributions

LNC designed the experiments, wrote the manuscript, and performed experiments RIR performed experiments, JCJ performed experiments, and FM designed and directed the experiments and wrote the manuscript. All of the authors analyzed the data, discussed the results and commented on the manuscript.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.FES Iztacala, Universidad Nacional Autónoma de MéxicoTlalnepantla de BazMexico

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