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INTRODUCTION: Depression frequently accompanied to Parkinson’s disease (PD). AIM(S): The aim of the study was to examine the effects of chronic treatment with amitriptyline(AMI) and L-DOPA on binding to dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in the substantia nigra (SN) and striatum (STR) of the unilaterally 6-OHDA-lesioned rats. METHOD(S): Experiments were performed on Wistar Han rats receiving unilaterally 16 µg/4 µl of 6-OHDA into the medial forebrain bundle (MFB). Two weeks later, rats exhibiting at least 100 contralateral turns/1 h in the apomorphine test were treated with AMI (10 mg/kg) and L-DOPA (12 mg/kg), alone or in combination, once daily for 21 consecutive days. The rats were sacrificed 1h after the last injection, their brains were dissected and frozen. The binding of [3H] GBR 12,935 to DAT, [3H] citalopram to SERT and [3H] nisoxetine to NET was assayed on nigral and striatal tissue sections. RESULTS: Injection of 6-OHDA into MFB caused a decline in [3H] GBR 12,935 binding to DAT in the ipsilateral SN and STR. On the contralateral side comes to up-regulation of DAT expression both in the STR and SN. AMI but not L-DOPA alone, lowered DAT expression in the contralateral STR. In the contralateral SN, DAT expression in drug treated groups was maintained at a control level. In the SN, the unilateral lesion of dopaminergic innervation caused a significant up-regulation of [3H] citalopram binding to SERT on both sides while in the STR only on the contralateral side. In both structures, L-DOPA did not change [3H] citalopram binding to SERT while AMI, alone or in combination, decreased it markedly on both sides. L-DOPA also decreased NET expression in the STR on both sides while AMI, alone or in combination maintained at the control level. CONCLUSIONS: Our data indicates that AMI can modulate the release of L-DOPA derived dopamine from serotonergic terminals on ipsilateral side and serotonin on contralateral one. The obtained data is discussed within the context of motor functions in PD.
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p.50
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- Department of Neuropsycho-pharmacology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
autor
- Department of Neuropsycho-pharmacology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
autor
- Department of Neuropsycho-pharmacology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
autor
- Department of Neuropsycho-pharmacology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
autor
- Department of Neuropsycho-pharmacology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
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