Depressive-like neurochemical and behavioral markers of Parkinson’s disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle

• Published in: Pharmacological reports 2017-10, Vol.69 (5), p.985-994
• Main Authors: Kamińska, Kinga, Lenda, Tomasz, Konieczny, Jolanta, Czarnecka, Anna, Lorenc-Koci, Elżbieta
• Format: Article
• Language: English
• Subjects: Animals; Asymmetric behavior; Behavior, Animal; Depressive Disorder - chemically induced; Depressive-like behavior; Dopamine - metabolism; Drug Safety and Pharmacovigilance; Male; Medial Forebrain Bundle - drug effects; Monoamine levels; Norepinephrine - metabolism; Original Article; Oxidopamine - toxicity; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - pathology; Pharmacotherapy; Pharmacy; Rats; Rats, Wistar; Serotonin - metabolism; Sucrose solution intake; Unilateral 6-OHDA lesion
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2017.05.016

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. 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. 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. Administration of the highest dose of 6-OHDA without desipramine pretreatment evoked neurochemical and behavioral changes resembling the advanced PD with coexisting depression.