The impact of l-dopa on attentional impairments in a rat model of Parkinson's disease.
Attentional deficits including difficulty in switching attention between tasks or rules, sustaining attention, and selectively attending to specific stimuli are commonly seen in patients with Parkinson's disease (PD). While these deficits are frequently reported, it is unclear how traditional dopamine replacement therapy such as l-dopa affects these deficits. In a rat model of PD in which dopamine is unilaterally depleted with a 6-hydroxydopamine infusion to the medial forebrain bundle, we first examined the impact of acute and chronic l-dopa treatment on attention switching as modeled by disengagement behavior (i.e. the ability to disengage from an on-going behavior such as eating or drinking to attend to perioral stimulation). Then, in a separate experiment, we evaluated the effects of l-dopa treatment on selective and sustained attention deficits using a five choice task. Our data suggest that the l-dopa dose necessary to recover motor function can successfully restore attention switching behavior (i.e. disengagement behavior), but further worsens performance in the selective and sustained attention task. Furthermore, this same dose was responsible for inducing dyskinesias in rats given chronic daily injections. Taken together, these findings demonstrate that dopamine replacement therapy may not be sufficient for treating all types of attentional dysfunction occurring in PD.
Department of Psychology, The University of Texas at Austin, United States.
Elizabeth S
ES
Smith
Department of Psychology, The University of Texas at Austin, United States.
Gwendolyn A
GA
Hardy
Department of Psychology, The University of Texas at Austin, United States.
Timothy
T
Schallert
Department of Psychology, The University of Texas at Austin, United States. Electronic address: leehj@austin.utexas.edu.
Hongjoo J
HJ
Lee
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley
D000978:Antiparkinson Agents; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine
Parkinson’s disease; disengagement behavior; l-dopa; selective and sustained attention