Pharmacological evidence that 5-HT2C receptor blockade selectively improves decision making when rewards are paired with audiovisual cues in a rat gambling task

Abstract

These findings demonstrate that the 5-HT receptor-mediated regulation of risky decision making and motor impulsivity can be pharmacologically dissociated and further show that the presence of highly salient reward-paired cues critically alters the neurochemical regulation of the choice process. Importantly, these results suggest that 5-HT receptor antagonists may be of use in disrupting maladaptive patterns of decision making.

Prior Exposure to Salient Win-Paired Cues in a Rat Gambling Task Increases Sensitivity to Cocaine Self-Administration and Suppresses Dopamine Efflux in Nucleus Accumbens: Support for the Reward Deficiency Hypothesis of Addiction

“…(1) ϭ 14.60, p Ͻ 0.001). As per results from previous studies (Barrus and Winstanley, 2016;Adams et al, 2017), animals trained on the cued rGT showed greater preference for the risky options (Table 1; cued vs uncued: choice ϫ task: F (3,119) ϭ 9.626, p Ͻ 0.0001; individual options: P1: t (46) ϭ 2.270, p ϭ 0.028; P2: t (46) ϭ 3.475, p ϭ 0.001; P3: t (46) ϭ Ϫ3.460, p ϭ 0.001; t (46) ϭ Ϫ2.134, p ϭ 0.038; score: task: F (1,46) ϭ 21.422, p Ͻ 0.0001). Similarly, as expected, riskpreferring rats showed a statistically significant increase in choice of the risky options (choice ϫ risk preference: F (3,124) ϭ 33.657, p Ͻ 0.0001; optimal versus risk preferring: P1: t (46) ϭ 2.186, p ϭ 0.035; P2: t (46) ϭ 8.632, p Ͻ 0.0001; P3: t (46) ϭ Ϫ5.914, p Ͻ 0.0001; P4: t (46) ϭ Ϫ3.963, p ϭ 0.0004; score: F (1,46) ϭ 171.198, p Ͻ 0.0001)…”

“…Each hole was associated with a different amount of reward (1-4 sugar pellets, P1-P4), length of penalty time-out (5-40 s), and probability of winning a reward over punishment (0.9 -0.4). The cued rGT was identical to the uncued task, except that reward delivery was paired with compound light/tone cues that scaled in complexity with the size of the win (Barrus and Winstanley, 2016;Adams et al, 2017). The reinforcement contingencies were designed such that consistent choice of options that yielded larger per trial gains (P3, P4) ultimately resulted in fewer sugar pellets over the course of a session due to the longer and more frequent time-out penalties incurred.…”

Increased motor impulsivity in a rat gambling task during chronic ropinirole treatment: potentiation by win-paired audiovisual cues

“…However, numerous studies have shown that choice patterns on the rGT are mutable by a variety of monoaminergic and catecholaminergic ligands (e.g., Adams et al 2017a;Baarendse et al 2012;Di Ciano et al 2018;Silveira et al 2015;Zeeb et al 2009). Choice on the uncued version of the rGT is sensitive to reinforcer devaluation, as would be expected if behavior was truly goal-directed rather than habitual or automatic .…”

“…The presence of audiovisual win-paired cues clearly potentiated the ability of ropinirole to enhance motor impulsivity, although how this happens remains unclear. The monoaminergic tone of the rat brain may be significantly different when engaged in the cued vs uncued rGT, as suggested by differential drug effects across the two task variants (Adams et al 2017a; Barrus and Winstanley 2016). The ability of damphetamine to enhance this form of motor impulsivity critically depends on dopamine release in the ventral striatum (Cole and Robbins 1989;Pattij et al 2007).…”

“…Subjects were trained to perform the Bstandard^uncued rGT (n = 24) or the cued rGT (n = 40) as described previously ( Fig. 1; Adams et al 2017a;Zeeb et al 2009Winstanley 2011, 2013). Each session lasted 30 min.…”