Interactions of the tricyclic antidepressant drug amitriptyline with L-DOPA in the striatum and substantia nigra of unilaterally 6-OHDA-lesioned rats. Relevance to motor dysfunction in Parkinson's disease

Publication date: Available online 2 October 2018Source: Neurochemistry InternationalAuthor(s): Kinga Kamińska, Tomasz Lenda, Jolanta Konieczny, Jadwiga Wardas, Elżbieta Lorenc-KociAbstractAntidepressant drugs are recommended for the treatment of Parkinson's disease (PD)-associated depression but their role in the modulation of L-DOPA-induced behavioral and neurochemical markers is poorly explored. The aim of the present study was to examine the impact of the tricyclic antidepressant amitriptyline and L-DOPA, administered chronically alone or in combination, on rotational behavior, monoamine levels and binding of radioligands to their transporters in the dopaminergic brain structures of unilaterally 6-OHDA-lesioned rats. Binding of [3H]nisoxetine to noradrenaline transporter (NET), [3H]GBR 12,935 to dopamine transporter (DAT) and [3H]citalopram to serotonin transporter (SERT) were analyzed by autoradiography. Amitriptyline administered alone did not induce rotational behavior but in combination with L-DOPA increased the number of contralateral rotations much more strongly than L-DOPA alone. The combined treatment also significantly increased the tissue dopamine (DA) content in the ipsilateral striatum and substantia nigra (SN) vs. L-DOPA alone. 6-OHDA-mediated lesion of nigrostriatal DA neurons drastically reduced DAT and NET bindings in the ipsilateral striatum. In the ipsilateral SN, DAT binding decreased while NET binding rose. SERT binding increased significantly mainly...
Source: Neurochemistry International - Category: Neuroscience Source Type: research