期刊
PHARMACOLOGICAL REPORTS
卷 69, 期 5, 页码 985-994出版社
POLISH ACAD SCIENCES INST PHARMACOLOGY
DOI: 10.1016/j.pharep.2017.05.016
关键词
Asymmetric behavior; Depressive-like behavior; Monoamine levels; Sucrose solution intake; Unilateral 6-OHDA lesion
资金
- European Union from the European Fund of Regional Development (EFRD) [POIG.01.01.02-12-004/09]
Background: Although Parkinson's disease (PD) is characterized by progressive neurodegeneration of multiple neurotransmitter systems, 6-hydroxydopamine (6-OHDA) as a model substance is mainly used to selectively damage the nigrostriatal dopaminergic neurons and induce parkinsonian-like motor disturbances in rats. We hypothesized that high doses of this neurotoxin affecting other monoaminergic systems may also evoke the depressive-like behavior. Methods: The impact of 6-OHDA (8, 12, 16 mu g/4 mu l) administered unilaterally into the medial forebrain bundle on the sucrose solution intake (a measure of anhedonia) and on the tissue levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the striatum (STR), substantia nigra (SN), prefrontal cortex (PFC) and hippocampus (HIP) was examined in rats pretreated or non-pretreated with desipramine. Results: The highest dose of 6-OHDA reduced the preference for 3% sucrose solution both in rats without and with desipramine pretreatment. All used doses of 6-OHDA dramatically decreased DA content in the studied brain structures on the ipsilateral side. NA levels were severely decreased in the ipsilateral STR, HIP and PFC of rats non-pretreated with desipramine and to a much lesser extent in those pretreated with desipramine. In the SN, moderate decreases in NA level were found both in rats pretreated and nonpretreated with desipramine. Higher doses of 6-OHDA reduced 5-HT content in the ipsilateral STR, HIP and PFC, but not in the SN, only in rats non-pretreated with desipramine. Conclusions: Administration of the highest dose of 6-OHDA without desipramine pretreatment evoked neurochemical and behavioral changes resembling the advanced PD with coexisting depression. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.
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