Medial prefrontal administration of MK-801 impairs T-maze discrimination reversal learning in weanling rats

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.

Figure 1

Schematic representation of cannula placements targeted to the prelimbic area of the mPFC in Experiment 1. Coordinates represent distances anterior to Bregma (Paxinos & Watson, 2005).

Figure 2

Mean (+SE) percentage of correct responses for the three treatment groups beginning on P26 in Experiment 1 as a function of training phase (acquisition or reversal), 12-trial blocks, and dose. During the reversal phase only, the mPFC treatment groups were vehicle (SALINE: open circles), or one of two drug doses (2.5 µg MK-801: closed circles; 5.0 µg MK-801: closed squares). All treatment groups received saline infusions during acquisition. Dashed line at 50 percent indicates chance performance.

Figure 3

Analysis of trials to criterion (TTC) and error types during reversal for P26 rats as a function of dose of MK-801 in Experiment 1. Mean (+SE) for TTC (A), total errors (B), perseverative errors (C), and regressive errors (D).

Figure 4

Schematic representation of cannula placements targeted to the prelimbic area of the mPFC in Experiment 2. Coordinates represent distances anterior to Bregma (Paxinos & Watson, 2005).

Figure 5

Mean (+SE) percentage of correct responses for the four MK-801 (2.5 µg) treatment groups in Experiment 2 beginning on P26 as a function of training phase (acquisition or reversal), 12-trial blocks, and treatment. The mPFC treatment groups were saline-saline (SAL-SAL: open circles), saline-MK-801 (SAL-MK: closed circles), MK-801-SAL (MK-SAL: open triangles), or MK-801-MK-801 (MK-MK: closed triangles). Dashed line at 50 percent indicates chance performance.

Figure 6

Analysis of trials to criterion and error types during reversal for P26 rats as a function of dose of MK-801 in Experiment 2. Differences were not found between a first (SAL-MK) or second (MK-MK) infusion of MK-801 during reversal, thus the SAL-MK and MK-MK treatment groups were pooled into Group MK (open bars), and the saline groups (MK-SAL and SAL-SAL) were pooled into Group SAL (closed bars). Mean (+SE) for TTC (A), total errors (B), perseverative errors (C), and regressive errors (D).