title: The effect of additional noradrenergic and serotonergic depletion on a lateralised choice reaction time task in rats with nigral 6-OHDA lesions.
abstract: Parkinson's disease (PD) patients often suffer from visuospatial deficits, which have been considered a disruption of the representation of external space. The lateralised choice reaction time (CRT) task is an operant task for rodents in which similar deficits can be assessed. It has been demonstrated that specific parameters in this task is disrupted after unilateral injections of 6-hydroxydopamine (6-OHDA), which have been associated with the dopamine (DA) depletion that inevitably follows this type of lesion. However, studies have demonstrated that this type of lesion also affects the serotonergic (5HT) and noradrenergic (NA) systems. However, the impact of these systems on parameters in the CRT task had not yet been investigated. To this end, rats were pretrained on the CRT task before receiving selective lesions of the DAergic system, either alone or in combination with depletion of the NA or 5HT system. All rats with a 6-OHDA lesion displayed a gradual decline in the selection, initiation and execution of lateralised movements compared to sham-lesion controls on the side contralateral to the lesion. They also displayed a reduced number of useable trials as well as an increased number of procedural errors. Interestingly, the group with an additional noradrenergic lesion was significantly slower in reacting to lateralised stimuli throughout the testing period compared to the other two groups with a 6-OHDA lesion. There was however no difference between the three different lesion groups in the other parameters assessed in the task. These data confirm previous findings demonstrating that the majority of the parameters assessed in the lateralised CRT task are strongly dependent on DA. However, this study has also shown that the NAergic system may play an important role in contributing to the attentive performance influencing the capacity to react to the presented lateralised stimuli.
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK. Electronic address: Hanna.Lindgren@med.lu.se.
authors: Hanna S
authors: HS
authors: Lindgren
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK.
authors: Merve
authors: M
authors: Demirbugen
authors: Department of Pharmacology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Filip
authors: F
authors: Bergqvist
authors: Welsh School of Pharmacy, Cardiff University, Cardiff, Wales, UK.
authors: Emma L
authors: EL
authors: Lane
authors: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK.
authors: Stephen B
authors: SB
authors: Dunnett
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count / Q000379:methods; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology*; D009068:Movement / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000172:deficiency*; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000172:deficiency*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013565:Sympatholytics / Q000633:toxicity; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D003891:Desipramine; D004298:Dopamine; D004299:Dopamine beta-Hydroxylase; D016666:Fluvoxamine; D009638:Norepinephrine; D016627:Oxidopamine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D013565:Sympatholytics; D014446:Tyrosine 3-Monooxygenase
keywords: 6-OHDA; Dopamine; Noradrenaline; Operant; Parkinson's disease; Serotonin