Depressive-like neurochemical and behavioral markers of Parkinson's disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle.
Pharmacol Rep
; 69(5): 985-994, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28843848
ABSTRACT
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, 16µg/4µl) 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 non-pretreated 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.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson Secundária
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Oxidopamina
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Transtorno Depressivo
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Feixe Prosencefálico Mediano
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article