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

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 μg/4 μl) 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. © 2017 institute of pharmacology,polish academy of sciences