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Neonatal co-lesion by DSP-4 and 5, 7-DHT produces adulthood behavioral sensitization to dopamine D2 receptor agonists

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Abstract

To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (50.0 mg/kg, sc) and 5, 7-dihydroxytryptamine (5, 7-DHT) (37.5 μg icv, half in each lateral ventricle), respectively, were administered to Wistar rats on the first and third days of postnatal ontogeny, and dopamine (DA) agonist-induced behaviors were assessed in adulthood. At eight weeks, using an HPLC/ED technique, DSP-4 treatment was associated with a reduction in NE content of the corpus striatum (> 60%), hippocampus (95%), and frontal cortex (> 85%), while 5, 7-DHT was associated with an 80-90% serotonin reduction in the same brain regions. DA content was unaltered in the striatum and the cortex. In the group lesioned with both DSP-4 and 5, 7-DHT, quinpirole-induced (DA D2 agonist) yawning, 7-hydroxy-DPAT-induced (DA D3 agonist) yawning, and apomorphine-induced (non-selective DA agonist) stereotypies were enhanced. However, SKF 38393-induced (DAD1 agonist) oral activity was reduced in the DSP-4 + 5, 7-DHT group. These findings demonstrate that DA D2- and D3-agonist-induced behaviors are enhanced while DA D1 -agonist-induced behaviors are suppressed in adult rats in which brain noradrenergic and serotoninergic innervation of the brain has largely been destroyed. This study indicates that noradrenergic and serotoninergic neurons have a great impact on the development of DA receptor reactivity (sensitivity).

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Authors and Affiliations

  1. Department of Pharmacology, Medical University of Silesia, Zabrze, Poland

    Przemysław Nowak, Dariusz Nitka, Adam Kwieciński, Jacek Drab & Ryszard Brus

  2. Department of Environmental Medicine, Epidemiology, Medical University of Silesia, Zabrze, Poland

    Jadwiga Jośko

  3. Department of Prosthetic Dentistry and, Medical University of Silesia, Zabrze, Poland

    Jacek Kasperski

  4. Clinic of Ophtalmology, Medical University of Silesia, Zabrze, Poland

    Dorota Pojda-Wilczek

  5. Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, USA

    Richard M. Kostrzewa

Authors
  1. Przemysław Nowak
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  2. Dariusz Nitka
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  3. Adam Kwieciński
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  4. Jadwiga Jośko
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  7. Jacek Kasperski
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  8. Richard M. Kostrzewa
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  9. Ryszard Brus
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Corresponding author

Correspondence to Przemysław Nowak.

Additional information

Part of this study was presented during XIV Days of Neuropsychopharmacology, Pharmacol Rep, 2005, 57, 260–261.

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Nowak, P., Nitka, D., Kwieciński, A. et al. Neonatal co-lesion by DSP-4 and 5, 7-DHT produces adulthood behavioral sensitization to dopamine D2 receptor agonists. Pharmacol. Rep 61, 311–318 (2009). https://doi.org/10.1016/S1734-1140(09)70037-4

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  • DOI: https://doi.org/10.1016/S1734-1140(09)70037-4

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