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

Area of Science:

• Neuroscience
• Toxicology
• Behavioral Science

Background:

• Chronic postweaning lead (Pb) exposure is linked to learning impairments.
• Neurochemical alterations, including enhanced dopamine (DA) activity and NMDA receptor blockade in the nucleus accumbens (NAC), are suspected contributors.
• The specific roles of NAC core and shell subregions in these effects remain unclear.

Purpose of the Study:

• To investigate if DA hyperactivity and/or NMDA receptor antagonism in the NAC mediate Pb-induced learning deficits.
• To determine the differential involvement of NAC core versus shell subregions.
• To ascertain if mimicking these neurochemical changes in control rats replicates Pb-induced learning impairments.

Main Methods:

• Infusion of DA, the NMDA antagonist MK-801, or combinations into the core or shell of the NAC in normal rats.
• Evaluation of effects on repeated learning (RL) and performance (P) accuracy and rate using a multiple schedule.
• Analysis of error types, specifically perseverative errors.

Main Results:

• In the NAC core, MK-801 selectively impaired RL accuracy by increasing perseverative errors, mimicking Pb effects.
• DA infusions caused non-specific accuracy reductions in both RL and P, reversible by higher MK-801 doses.
• In the NAC shell, MK-801 reduced accuracy in both RL and P, while DA had no systematic effects.

Conclusions:

• The NAC core is more critical than the shell for mediating spatial sequence learning.
• Inhibition of glutamatergic NMDA function in the NAC core plays a key role in Pb-induced learning impairments.
• These findings suggest specific neurochemical targets for mitigating lead toxicity effects on cognition.