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Published on: February 26, 2012
Medial prefrontal administration of MK-801 impairs T-maze discrimination reversal learning in weanling rats
Deborah J Watson1, Mark E Stanton
1University of Delaware, Department of Psychology, Newark, DE 19716, United States. dwatson@psych.udel.edu
Abstract:
Several executive functions rely on the medial prefrontal cortex (mPFC) in the rat. Aspiration and neurotoxic lesions of the mPFC impair reversal learning in adult rats. Systemic administration of MK-801, an NMDA-receptor antagonist, impairs T-maze reversal learning in weanling rats but the role of mPFC NMDA-receptor antagonism in this effect is not known in either adult or young animals. This set of studies showed that mPFC NMDA receptors are specifically involved in T-maze discrimination reversal in weanling rats. In Experiment 1, 26-day-old rats (P26) demonstrated a dose-dependent impairment following bilateral mPFC administration of either 2.5 or 5.0microg MK-801 or saline (vehicle) during the reversal training phase only. In Experiment 2, P26 rats were trained on the same task, but four groups of rats received bilateral mPFC infusions during acquisition only (MK-SAL), reversal only (SAL-MK), both phases (MK-MK), or neither phase (SAL-SAL). MK-801 impaired performance only when infused during reversal. This suggests that NMDA-receptor antagonism in the mPFC is selectively involved in reversal learning during development and this may account for the previously reported effects of systemic MK-801 on T-maze discrimination reversal in weanling rats.
Insights
Medial prefrontal cortex (mPFC) NMDA receptors are crucial for T-maze reversal learning in young rats. Blocking these receptors specifically during the reversal phase impairs performance, highlighting their developmental role.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Cognitive Neuroscience
Background:
- The medial prefrontal cortex (mPFC) is vital for executive functions, including reversal learning.
- Previous studies show lesions or NMDA-receptor antagonist administration impair reversal learning in adult and weanling rats, respectively.
- The specific role of mPFC NMDA receptors in early-life reversal learning remains unclear.
Purpose of the Study:
- To investigate the involvement of medial prefrontal cortex (mPFC) NMDA receptors in T-maze discrimination reversal learning in developing rats.
- To determine if NMDA-receptor antagonism in the mPFC underlies the effects of systemic MK-801 on reversal learning in weanling rats.
Main Methods:
- Bilateral infusions of the NMDA-receptor antagonist MK-801 or saline into the mPFC of 26-day-old rats (P26).
- Experiment 1: Dose-dependent effects of MK-801 administered during the reversal phase.
- Experiment 2: Infusions during acquisition, reversal, both, or neither phase of T-maze training.
Main Results:
- Direct mPFC administration of MK-801 dose-dependently impaired T-maze reversal learning in P26 rats.
- Performance deficits were observed only when MK-801 was infused during the reversal training phase, not during acquisition.
- These findings indicate a specific role for mPFC NMDA receptors in the reversal learning process during development.
Conclusions:
- NMDA-receptor antagonism within the mPFC is selectively critical for T-maze discrimination reversal learning in weanling rats.
- This targeted effect likely explains the previously observed impairments from systemic MK-801 administration in young animals.
- The study elucidates a specific developmental function of mPFC NMDA receptors in cognitive flexibility.
