Pramipexole but not imipramine or fluoxetine reverses the "depressive-like" behaviour in a rat model of preclinical stages of Parkinson's disease.

Abstract

Depression is a frequent comorbid disorder in Parkinson's disease and may antedate its motor symptoms. However, mechanisms underlying Parkinson's disease-associated depression are unknown and its current medication is insufficient. The aim of the present study was to compare antidepressant-like effects of imipramine, fluoxetine and pramipexole in a model of preclinical stages of Parkinson's disease in rats. 6-Hydroxydopamine was bilaterally injected into the ventrolateral region of the caudate-putamen in rats. This treatment induced moderate decreases in the levels of dopamine and its metabolites in the caudate-putamen, nucleus accumbens and frontal cortex and reduced the density of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta and ventral tegmental area. The lesion increased immobility measured in the forced swimming test without influencing locomotor activity. Chronic (13 days) administration of pramipexole (1mg/kg sc/twice a day) reversed prolongation of the immobility time in lesioned animals but did not stimulate their locomotion. Chronic pramipexole activated dopaminergic transmission in the brain structures which might contribute to its effectiveness in the forced swimming test. In contrast, the 13-day administration of imipramine (10mg/kg ip/day) and fluoxetine (10mg/kg ip/day) did not shorten the immobility time in lesioned rats but reduced their locomotion. The present study indicates that already a moderate lesion of dopaminergic neurons induces "depressive-like" behaviour in animals which is reversed by chronic administration of the antiparkinsonian drug, pramipexole.

• Authors: Klemencja Berghauzen-Maciejewska, Katarzyna Kuter, Wacław Kolasiewicz, Urszula Głowacka, Anna Dziubina, Krystyna Ossowska, Jadwiga Wardas
• Journal: Behavioural brain research (Behav Brain Res) Vol. 271 Pg. 343-53 (Sep 01 2014) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 24956561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antidepressive Agents
• Benzothiazoles
• Dopamine Agonists
• Fluoxetine
• Pramipexole
• Oxidopamine
• Imipramine

Topics

• Animals
• Antidepressive Agents (pharmacology)
• Benzothiazoles (pharmacology)
• Depression (drug therapy, etiology, psychology)
• Disease Models, Animal
• Dopamine Agonists (pharmacology)
• Fluoxetine (pharmacology)
• Imipramine (pharmacology)
• Male
• Motor Activity (drug effects)
• Oxidopamine (poisoning)
• Parkinson Disease (complications, psychology)
• Pramipexole
• Rats
• Rats, Wistar
• Swimming (psychology)
• Treatment Outcome