Effect of coadministration of the GABAB agonist baclofen and the 5-HT2C agonist Ro60-0175 on the expression of amphetamine-induced locomotor sensitization
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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.
KeywordsAmphetamine Locomotor sensitization Baclofen
This study was supported by grant IN301717 from PAPIIT-UNAM (Mexico).
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.
- Acosta-García J, Jimenez JC, Miranda F (2017) Additive effects of coadministration of A2A receptor agonist CGS-21680 and mGluR5 antagonist MPEP on the development and expression of methamphetamine-induced locomotor sensitization in rats. J Drug Alcohol Res 6:1–11. https://doi.org/10.4303/jdar/236038 CrossRefGoogle Scholar
- Bartoletti M, Gubellini C, Ricci F, Gaiardi M (2005) Baclofen blocks the development of sensitization to the locomotor stimulant effect of amphetamine. Behav Pharmacol 16:553–558. https://doi.org/10.1097/01.fbp.0000179279.98029.e9 CrossRefGoogle Scholar
- Cathala A, Devroye C, Maitre M, Piazza PV, Abrous DN, Revest JM, Spampinato U (2015) Serotonin2C receptors modulate dopamine transmission in the nucleus accumbens independently of dopamine release: behavioral, neurochemical and molecular studies with cocaine. Addict Biol 20(3):445–457. https://doi.org/10.1111/adb.12137 CrossRefGoogle Scholar
- Cedillo LN, Miranda F (2013) Effects of co-administration of the GABAB receptor agonist baclofen and a positive allosteric modulator of the GABAB receptor, CGP7930, on the development and expression of amphetamine-induced locomotor sensitization in rats. Pharmacol Rep 65(5):1132–1143CrossRefGoogle Scholar
- Kalivas PW, Duffy P, Eberhardt H (1990) Modulation of A10 neurons by gamma-aminobutyric acid agonist. J Pharmacol Exp Ther 253:858–866Google Scholar
- Miranda F, Jiménez JC, Cedillo LN, Sandoval-Sánchez A, Millán-Mejía P, Sánchez-Castillo H, Velázquez-Martínez DN (2009) The GABA-B antagonist 2-hydroxysaclofen reverses the effects of baclofen on the discriminative stimulus effects of d-amphetamine in the conditioned taste aversion procedure. Pharmacol Biochem Behav 93:25–30. https://doi.org/10.1016/j.pbb.2009.04.002 CrossRefGoogle Scholar
- Navailles S, Moison D, Cunningham KA, Spampinato U (2008) Differential regulation of the mesoaccumbens dopamine circuit by serotonin2C receptors in the ventral tegmental area and the nucleus accumbens: an in vivo microdialysis study with cocaine. Neuropsychopharmacology 33:237–246. https://doi.org/10.1038/sj.npp.1301414 CrossRefGoogle Scholar
- Pinheiro CM, Carey RJ, Cruz DFR, Wermelinger ML (2011) Reversal of apomorphine locomotor sensitization by a single post-conditioning trial treatment with a low autoreceptor dose of apomorphine: a memory re-consolidation approach. Pharmacol Biochem Behav 99:29–34. https://doi.org/10.1016/j.pbb.2011.03.018 CrossRefGoogle Scholar
- Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95:91–117Google Scholar
- Shoaib M, Swanner LS, Beyer CE, Goldberg SR, Schindler CW (1998) The GABAB agonist baclofen modifies cocaine self-administration in rats. Behav Pharmacol 9:195–206Google Scholar
- Wu X, Pang G, Zhang YM, Li G, Xu S, Dong L, Stackman RW, Zhang G (2015) Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Neurosci Lett 607:23–28. https://doi.org/10.1016/j.neulet.2015.09.013 CrossRefGoogle Scholar
- Xi ZX, Stein EA (1999) Baclofen inhibits heroin self-administration behavior and mesolimbic dopamine release. J Pharmacol Exp Ther 290:1369–1374Google Scholar