Cognitive Deficit Caused by Regional Depletion of Dopamine in Prefrontal Cortex of Rhesus Monkey

Abstract

Depletion of dopamine in a circumscribed area of association cortex in rhesus monkeys produces an impairment in spatial delayed alternation performance nearly as severe as that caused by surgical ablation of the same area. This behavioral deficit can be pharmacologically reversed with dopamine agonists such as L-dopa and apomorphine. These data provide direct evidence that dopamine plays an important role in a specific cortical function.

Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion

“…These data correspond to reports of cognitive disturbances in schizophrenic subjects (Fey 1951;Goldman-Rakic 1991;Park and Holzman 1992), and recent in vivo imaging studies of the schizophrenic brain have revealed a failure of activation of frontal cortex during cognitive performance (termed "hypofrontality" by Weinberger and Berman 1996), effects that may be mediated by dopaminergic dysfunction Daniel et al 1989Daniel et al , 1991Dolan et al 1995). These data are also consistent with studies in nonhuman primates that have revealed that lesions of the prefrontal cortical dopamine innervation lead to working memory impairments (Brozoski et al 1979), a cognitive process closely associated with this brain region (Goldman-Rakic 1987).…”

Targeting the dopamine D1 receptor or its downstream signalling by inhibiting phosphodiesterase‐1 improves cognitive performance

“…Lesions of the mesocortical dopaminergic projection have long been known to impair working memory performance, as previously shown in monkeys (Brozoski et al, 1979). http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=214, but not http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=215, antagonists impair delay‐dependent working memory performance when infused into substructures of the primate prefrontal brain (Sawaguchi and Goldman‐Rakic, 1991).…”

Extended Access to Cocaine Self-Administration Produces Long-Lasting Prefrontal Cortex-Dependent Working Memory Impairments

“…To test these hypotheses, the integrity of working memory under high and low cognitive demands and high-and low-incentive conditions was assessed in rats with a history of extended or limited access to cocaine 3-17 days after the last self-administration session. Working memory under high incentive and cognitive demands was measured in food-restricted rats using a delayed nonmatching-to-sample procedure, a task sensitive to prefrontal cortical dysfunction (Divac, 1971;Brozoski et al, 1979;Jacobsen, 1936;Mishkin and Pribram, 1956;Simon et al, 1980;Aggleton et al, 1995;Walton et al, 2003). Specifically, the percentage of correct responses in this task is decreased after dmPFC lesion, particularly when a delay is used to increase the working memory load.…”