Monoaminergic modulation of decision-making under risk of punishment in a rat model

Abstract

The ability to decide advantageously among options that vary in both their risks and rewards is critical for survival and well-being. Previous work shows that some forms of risky decision-making are robustly modulated by monoamine signaling, but it is less clear how monoamine signaling modulates decision-making under risk of explicit punishment. The goal of these experiments was to determine how this form of decision-making is modulated by dopamine, serotonin, and norepinephrine signaling, using a task in which rats choose between a small, 'safe' food reward and a large food reward associated with variable risks of punishment. Preference for the large, risky reward (risk-taking) was reduced by administration of a D2/3 dopamine receptor agonist (bromocriptine) and a selective D2 agonist (sumanirole). The selective D3 agonist PD128907 appeared to attenuate reward discrimination abilities but did not affect risk-taking per se. In contrast, drugs targeting serotonergic and noradrenergic signaling had few if any effects on choice behavior. These data suggest that in contrast to other forms of risky decision-making, decision-making under risk of punishment is selectively modulated by dopamine signaling, predominantly through D2 receptors.

Figure 1.. Dopaminergic modulation of risky decision making.

(A) Bromocriptine (D2/D3 receptor agonist) decreased choice of the large, risky reward (decreased risky choice). (B) Sumanirole (D2 receptor agonist) caused a near-significant decrease in risky choice. (C) PD128907 (D3 receptor agonist) decreased risky choice, although this effect appeared due to an impairment in reward discrimination. (D) L-741,626 (D2 receptor antagonist) did not affect risky choice. (E) SB-277011-A (D3 receptor antagonist) did not affect risky choice,. Data are represented as mean % choice of the large, risky reward ± SEM.

Figure 2.. Serotonergic modulation of risky decision making.

(A) Citalopram (selective serotonin reuptake inhibitor) did not affect choice of the large, risky reward (risky choice). (B) M100907 (5-HT2A receptor antagonist) did not affect risky choice. (C) SB 242,084 (5-HT2C receptor antagonist) did not affect risky choice. (D) WAY 100635 (5-HT1A receptor antagonist) did not affect risky choice. (E) 8-OH-DPAT (5-HT1A receptor agonist) decreased risky choice, but this effect appeared largely due to an impairment in reward discrimination. Data are represented as mean % choice of the large, risky reward ± SEM.

Figure 3:. Noradrenergic modulation of risky decision making.

A) Atomoxetine (norepinephrine reuptake inhibitor) did not affect choice of the large, risky reward. Data are represented as % mean choice of the large, risky reward ± SEM.