Medial prefrontal cortex lesions impair decision-making on a rodent gambling task: reversal by D1 receptor antagonist administration

Abstract

Decision-making is a complex cognitive process that is impaired in a number of psychiatric disorders. In the laboratory, decision-making is frequently assessed using "gambling" tasks that are designed to simulate real-life decisions in terms of uncertainty, reward and punishment. Here, we investigate whether lesions of the medial prefrontal cortex (PFC) cause impairments in decision-making using a rodent gambling task (rGT). In this task, rats have to decide between 1 of 4 possible options: 2 options are considered "advantageous" and lead to greater net rewards (food pellets) than the other 2 "disadvantageous" options. Once rats attained stable levels of performance on the rGT they underwent sham or excitoxic lesions of the medial PFC and were allowed to recover for 1 week. Following recovery, rats were retrained for 5 days and then the effects of a dopamine D1-like receptor antagonist (SCH23390) or a D2-like receptor antagonist (haloperidol) on performance were assessed. Lesioned rats exhibited impaired decision-making: they made fewer advantageous choices and chose the most optimal choice less frequently than did sham-operated rats. Administration of SCH23390 (0.03 mg/kg), but not haloperidol (0.015-0.03 mg/kg) attenuated the lesion-induced decision-making deficit. These results indicate that the medial PFC is important for decision-making and that excessive signaling at D1 receptors may contribute to decision-making impairments.

Figure 1

The location and extent of ibotenic acid lesions of the medial prefrontal cortex (PFC). A) Schematic showing the largest (grey) and smallest (black) extent of the lesion on any particular section through the medial PFC. B) Photomicrograph depicting the average extent of damage caused by ibotenic acid infusions. Adapted from [24].

Figure 2

Effects of medial PFC lesions on performance in the rodent gambling task. A) % Advantageous responses. Lesioned rats exhibit a decrease in their choice of advantageous options that progressively worsened across testing. B) % Choice of each hole (H). All rats chose hole 2 (most optimal) more than they chose the other 3 options. Lesioned rats chose hole 3 more frequently than sham-operated rats on post-lesion days 1, 4 and 5 and chose hole 1 less frequently than sham-operated rats on post-lesion day 3. There was no effects of either condition or day of testing on the % Omissions (C), the % Premature responses (D), or the number of magazine entries made (E). *P < 0.05 sham-operated vs lesion; ^#P < 0.05 lesion compared to baseline; ^P < 0.05 both groups compared to baseline; ^‡P < 0.5, sham-operated vs lesion hole 1; ^†P < 0.05 sham-operated vs lesion hole 3; ^∞P < 0.05 hole 2 vs all other holes.

Figure 3

Effects of SCH23390 on choice behavior in the rodent gambling task. A) Lesioned rats chose the advantageous holes less frequently than sham-operated rats; this effect was attenuated by SCH23390 administration. B) All rats chose hole 2 more frequently than all other holes. In addition sham-operated rats chose hole 2 more frequently than lesioned rats. SCH23390 did not affect hole choice. C) SCH23390 increased the % omissions in lesioned, but not sham-operated, rats. D) SCH23390 administration significantly decreased the % premature responding; this effect was potentiated in lesioned rats. E) SCH23390 administration significantly reduced the number of magazine entries. *P < 0.05 sham-operated vs lesion; ^#P < 0.05 lesion compared to baseline; ^P < 0.05 both groups compared to baseline; ^∞P < 0.05 hole 2 vs all other holes.

Figure 4

Effects of haloperidol on choice behavior in the rodent gambling task. A) Lesioned rats chose the advantageous holes less frequently than sham-operated rats; this effect was not affected by haloperidol administration. B) All rats chose hole 2 more than all other holes. In addition sham-operated rats chose hole 2 more frequently and chose hole 3 less frequently than lesioned rats. Haloperidol did not affect hole choice. C) Haloperidol did not affect % omissions. D) Haloperidol (0.03 mg/kg) increased the % premature responding. E) There was a tendency for lesioned rats to make more magazine entries than sham-operated rats; this was not affected by haloperidol administration. *P < 0.05 sham-operated vs lesion; ^#P < 0.05 lesion compared to baseline; ^P < 0.05 both groups compared to baseline; ^∞P < 0.05 hole 2 vs all other holes.