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Interaction between the noradrenergic and serotonergic systems in locomotor hyperactivity and striatal expression of Fos induced by amphetamine in rats

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Abstract

It is classically considered that Amphetamine acts by increasing extracellular dopamine levels. However, some data suggest a relevant role of other neurochemical systems. The striatum is of particular interest to the study of this question. We have investigated the involvement of the noradrenergic and serotonergic systems and their possible interaction in the striatal responses to Amphetamine using a double behavioral and immunohistochemical approach (i.e., changes in locomotor activity and striatal expression of Fos). In normal rats, Amphetamine induced locomotor hyperactivity and striatal expression of Fos. Pretreatment with the α1-adrenergic-receptor antagonist Prazosin or lesion of the serotonergic system significantly reduced the locomotor hyperactivity and striatal Fos expression induced by Amphetamine. Administration of Prazosin to rats with serotonergic denervation did not produce any further reduction in the Amphetamine-induced locomotor hyperactivity or striatal Fos expression compared with that observed in rats with serotonergic denervation only. Amphetamine did not induce a detectable increase in Fos expression in dopamine-denervated striata, and elicited intense rotation towards the dopamine-denervated side. This suggests that striatal dopamine release is essential in the Amphetamine-induced effects on striatal neurons. However, the noradrenergic system plays an important role, and the serotonergic system is necessary for mediating the effects of the Amphetamine-induced noradrenergic stimulation. Concurrent stimulation of dopaminergic and serotonergic receptors appears necessary to regulate Amphetamine-induced responses in the striatal neurons.

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Acknowledgements

This work was supported by grants from XUGA and the Spanish DGESIC (PGC).

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Authors and Affiliations

  1. Laboratory of Neuroanatomy and Experimental Neurology, Dept. of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Spain

    A. Muñoz, A. Lopez-Real, J. L. Labandeira-Garcia & M. J. Guerra

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  1. A. Muñoz
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  2. A. Lopez-Real
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  3. J. L. Labandeira-Garcia
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  4. M. J. Guerra
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Correspondence to J. L. Labandeira-Garcia.

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Muñoz, A., Lopez-Real, A., Labandeira-Garcia, J.L. et al. Interaction between the noradrenergic and serotonergic systems in locomotor hyperactivity and striatal expression of Fos induced by amphetamine in rats. Exp Brain Res 153, 92–99 (2003). https://doi.org/10.1007/s00221-003-1582-6

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