The influence of imipramine and pramipexole on depressivelike behaviour in an animal model of a pre-clinical stage of Parkinson’s disease

• Autorzy: Berghauzen K. , Wardas J. , Kuter K. , Kolasiewicz W. , Glowacka U. , Ossowska K.
• Języki publikacji: EN

Abstrakty

EN

Motor disturbances in Parkinson’s disease (PD) results from the massive degeneration of dopaminergic neurons and terminals of the nigrostriatal pathway and a decrease in the dopamine (DA) level in the caudate nucleus and putamen. The clinical phase of PD is preceded by a preclinical period where depression is a frequent comorbid disturbance.Dysfunctions of monoaminergic systems could underlie depression in PD. Clinical trials suggest that a treatment with tricyclic antidepressant drugs can be effective in ameliorating depression in PD. Moreover, recent studies have suggested that the administration of pramipexole (the mixed dopamine D2/D3 receptor agonist) may reduce not only motor symptoms (akinesia, rigidity and tremor at rest) but also depression in PD. The aim of the study was to examine the influence of classic tricyclic antidepressant -imipramine and pramipexole on the ‘depressivelike’ behaviour of rats with moderate lesion of the nigrostriatal system. Male Wistar rats were injected bilaterally with 6-OHDA (3.75–15 µg/2.5 µl) into the ventral striatum (vSTR). Imipramine was injected i.p. at a dose of 10 mg/kg once a day and pramipexole s.c. at a dose of 1 mg/kg twice a day for 14 days. The locomotor activity in actometers and behaviour of rats in the forced swimming test (FS) were measured on the 15th day after the surgery. The lesion extent was analysed by HPLC and immunohistochemically. The lesion increased immobility and swimming and decreased climbing in FS, however, it did not influence the locomotor activity of rats. All the lesion-induced disturbances observed in FS were decreased by pramipexole. Imipramine increased only climbing, but had no influence on immobility in lesioned rats. Moreover, imipramine but not pramipexole reduced the locomotor activity in lesioned animals. After the administration of 6-OHDA levels of DA decreased (ca. 45%) in the dorsal striatum (dSTR), vSTR and frontal cortex (FCX). Pramipexole and imipramine injections had no influence on DA levels in lesioned rats. Levels of DA metabolites (DOPAC, HVA) were markedly increased in dSTR and vSTR after injections of pramipexole. Moreover, pramipexole significantly increased the turnover of DOPAC/DA and HVA/DA in dSTR and vSTR in sham-operated and lesioned rats. These results indicate that a relatively moderate dopaminergic lesion which does not produce any motor disturbances, may induce “depressive-like” symptoms which are reversed by dopamine agonist but not by a classic antidepressant. Acknowledgments Study supported by the Project “Depression-Mechanisms-Therapy” (POIG.01.01.02-12-004/09-00), co-financed by EU from the European Regional Development Fund as a part of the Operational Programme “Innovative Economy 2007-2013”

Słowa kluczowe

EN

human disease; imipramine; pramipexole; depression-like behaviour; animal model; preclinical stage; Parkinson's disease; motor disturbance; degeneration; dopamine level

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.192

Twórcy

autor

Berghauzen K.

• Department of Neuro- and Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Wardas J.

• Department of Neuro- and Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Kuter K.

• Department of Neuro- and Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Kolasiewicz W.

• Department of Neuro- and Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Glowacka U.

• Department of Neuro- and Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Ossowska K.

• Department of Neuro- and Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland