BACKGROUND AND AIMS: The objective of the present study was to examine rotational behavior and monoamine metabolism in motor (striatum, STR; substantia nigra, SN) and limbic (prefrontal cortex, PFC; hippocampus, HIP) brain structures of unilaterally 6-OHDA-lesioned rats treated chronically with the chosen selective serotonin reuptake inhibitors (SSRIs): fluoxetine or paroxetine alone or jointly with L-DOPA. METHODS: The experiment was performed on male Wistar rats injected unilaterally with 6-OHDA (16 μg/4 μl) into the medial forebrain bundle. Two weeks later, the animals were tested for the rotational behavior induced by apomorphine. Rats exhibiting more than 100 contralateral turns/1 h were administered fluoxetine (5 mg/kg) or paroxetine (5 mg/kg) and L-dopa (12 mg/kg), alone or in combination, once daily for 21 consecutive days. Rotational behavior was recorded after the first and the penultimate doses of the examined drugs. The levels of dopamine (DA), serotonin (5-HT), and their metabolites were determined in the tissue homogenates of motor and limbic brain structures 1h after the last drug injections using HPLC method. RESULTS: Chronic combined administration of fluoxetine+L-DOPA significantly increased while paroxetine+L-DOPA decreased the number of contralateral rotations compared to the group receiving L-DOPA alone. L-DOPA given alone or jointly with SSRIs increased DA levels on both sides of all the examined structures. Fluoxetine intensified L-DOPA effect in the HIP while paroxetine in the SN. Joint administration of fluoxetine+L-DOPA decreased 5-HT level in the ipsilateral SN more distinctly than each of these drugs alone. Paroxetine+L-DOPA evoked similar decreases in tissue 5-HT content in the ipsilateral STR, HIP and PFC. CONCLUSION: The obtained data are discussed in the context of motor and psychiatric disturbances observed in Parkinson’s disease. The study was supported by the Project “Depression-MechanismsTherapy” – POIG.01.01.02-12-004/09-00.
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