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Kamińska, Kinga; Lenda, Tomasz; Konieczny, Jolanta; Lorenc-Koci, Elżbieta

Behavioral and neurochemical interactions of the tricyclic antidepressant drug desipramine with L-DOPA in 6-OHDA-lesioned rats. Implications for motor and psychiatric functions in Parkinson’s disease

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  • Medientyp: E-Artikel
  • Titel: Behavioral and neurochemical interactions of the tricyclic antidepressant drug desipramine with L-DOPA in 6-OHDA-lesioned rats. Implications for motor and psychiatric functions in Parkinson’s disease
  • Beteiligte: Kamińska, Kinga; Lenda, Tomasz; Konieczny, Jolanta; Lorenc-Koci, Elżbieta
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Psychopharmacology
  • Sprache: Englisch
  • DOI: 10.1007/s00213-022-06238-x
  • ISSN: 0033-3158; 1432-2072
  • Schlagwörter: Pharmacology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Rationale</jats:title> <jats:p>The pharmacological effects of antidepressants in modulating noradrenergic transmission as compared to serotonergic transmission in a rat model of Parkinson’s disease under chronic L-DOPA therapy are insufficiently explored.</jats:p> </jats:sec><jats:sec> <jats:title>Objectives</jats:title> <jats:p>The aim of the present study was to investigate the effect of the tricyclic antidepressant desipramine administered chronically alone or jointly with L-DOPA, on motor behavior and monoamine metabolism in selected brain structures of rats with the unilateral 6-OHDA lesion.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>The antiparkinsonian activities of L-DOPA and desipramine were assessed behaviorally using a rotation test and biochemically based on changes in the tissue concentrations of noradrenaline, dopamine and serotonin and their metabolites, evaluated separately for the ipsi- and contralateral motor (striatum, substantia nigra) and limbic (prefrontal cortex, hippocampus) structures of rat brain by HPLC method.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Desipramine administered alone did not induce rotational behavior, but in combination with L-DOPA, it increased the number of contralateral rotations more strongly than L-DOPA alone. Both L-DOPA and desipramine + L-DOPA significantly increased DA levels in the ipsilateral striatum, substantia nigra, prefrontal cortex and the ipsi- and contralateral hippocampus. The combined treatment also significantly increased noradrenaline content in the ipsi- and contralateral striatum, while L-DOPA alone decreased serotonin level on both sides of the hippocampus.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The performed analysis of the level of monoamines and their metabolites in the selected brain structures suggests that co-modulation of noradrenergic and dopaminergic transmission in Parkinson’s disease by the combined therapy with desipramine + L-DOPA may have some positive implications for motor and psychiatric functions but further research is needed to exclude potential negative effects.</jats:p> </jats:sec>