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National Institute of Environmental Health Sciences

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Publication Detail

Title: Glutamate and dopamine in nucleus accumbens core and shell: sequence learning versus performance.

Authors: Bauter, M R; Brockel, B J; Pankevich, D E; Virgolini, M B; Cory-Slechta, D A

Published In Neurotoxicology, (2003 Mar)

Abstract: This study sought to determine whether neurochemical changes associated with chronic postweaning lead (Pb) exposure, namely, enhanced dopamine (DA) activity and/or blockade of NMDA function in nucleus accumbens (NAC), underlie the learning impairments also associated with this Pb regimen, and whether core or shell subregions of nucleus accumbens would be more important to such effects. If so, then mimicking these neurochemical changes in normal (control) rats should reproduce these Pb-induced learning impairments. For this purpose, the effects of DA (20-80 microg), the non-competitive NMDA antagonist MK-801 (1.0-2.5 microg) or DA+MK-801 (40+1.0, 80+2.5 microg) were infused in core or shell of nucleus accumbens in normal rats and effects on a multiple schedule of repeated learning (RL) and performance (P) evaluated. In core, MK-801 mimicked the effects of Pb exposure, selectively reducing RL accuracy with no corresponding changes in P accuracy, an effect derived from an increased frequency of perseverative errors. DA produced non-specific changes, reducing accuracy levels in RL and P components. Accuracy and rate effects of DA could be reversed by concurrent administration of the higher MK-801 dose. In shell, MK-801, primarily the lower dose, reduced accuracy in both the RL and P components, while DA did not produce any systematic effects. Collectively, these results point to a greater importance of core as compared to shell in the mediation of learning of spatial sequences, and suggest that inhibition of glutamatergic NMDA function may play a critical role in the selective learning impairments associated with chronic low level Pb exposure.

PubMed ID: 12606295 Exiting the NIEHS site

MeSH Terms: Animals; Behavior, Animal/drug effects; Behavior, Animal/physiology; Conditioning, Operant/drug effects; Dizocilpine Maleate/administration & dosage; Dizocilpine Maleate/pharmacology; Dopamine/administration & dosage; Dopamine/metabolism*; Dopamine/pharmacology; Dopamine/physiology; Excitatory Amino Acid Antagonists/administration & dosage; Excitatory Amino Acid Antagonists/pharmacology; Glutamic Acid/metabolism*; Glutamic Acid/physiology; Lead Poisoning, Nervous System/metabolism; Lead Poisoning, Nervous System/pathology; Lead Poisoning, Nervous System/psychology; Lead/blood; Limbic System/physiology; Male; Microinjections; Nucleus Accumbens/drug effects; Nucleus Accumbens/metabolism*; Nucleus Accumbens/pathology; Psychomotor Performance/drug effects; Psychomotor Performance/physiology*; Rats; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate/metabolism; Research Support, U.S. Gov't, P.H.S.; Serial Learning/drug effects; Serial Learning/physiology*

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