Activation of dopamine D4 receptors within the anterior cingulate cortex enhances the erroneous expectation of reward on a rat slot machine task

The β‐adrenoceptor blocker propranolol ameliorates compulsive‐like gambling behaviour in a rodent slot machine task: implications for iatrogenic gambling disorder

“…Chronic DA agonism may simulate increased tonic DA levels, potentially obfuscating these temporary dips and impair learning from negative outcomes (Grace, ; Schultz, ; Goto et al ., ). Drawing parallels between these findings and rSMT performance, intact animals experience loss trials as aversive or frustrating, and such trials prompt disengagement with the task (Cocker et al ., ). Following ropinirole treatment, the latency to respond after near‐miss trials is statistically equivalent to any other trial type and there is a general decrease in latency to respond at the apertures, even when the previous light set to off, signalling no reward would be available.…”

“…Rodent models likewise indicate that repeated administration of D 2 ‐family agonists induce compulsive‐like behaviour and enhance choice of uncertain outcomes (Szechtman et al ., ; Rokosik & Napier, ; Eagle et al ., ). We have shown that behaviour on a rodent slot machine task (rSMT) is critically mediated by the D 2 receptor family (Winstanley et al ., ; Cocker et al ., , ) and chronic administration of the D 2 ‐like agonist ropinirole, a drug that has previously been associated with iatrogenic gambling in PD (Dodd et al ., ), leads to a robust increase in the number of trials completed on the rSMT (Cocker et al ., ). This invigoration of behaviour may be analogous to the increased game engagement and compulsive play exhibited by PD patients with iatrogenic GD.…”

Gambling disorder: an integrative review of animal and human studies

“…D 2 and D 4 receptor agonists affected the reward expectancies in the rSMT measured by increases in cash out responses during near‐miss trials . The effects of the D 4 agonist are modulated, at least in part, through signaling in the anterior cingulate cortex . In humans, mesolimbic circuits have also been implicated in this type of cognitive distortion, with heightened activity seen in cortical mesolimbic regions during near‐miss events in fMRI studies .…”

Elucidating the role of D4 receptors in mediating attributions of salience to incentive stimuli on Pavlovian conditioned approach and conditioned reinforcement paradigms

“…Indeed, this study was, in part, motivated by recent findings on the rSMT that suggested D 4 receptors are critically involved in mediating attributions of salience to reward-related stimuli during gambling-like decision making [21,22]. Consequently, we have speculated that targeting these receptors could represent a potential pharmacotherapy for GD [23].…”

“…During complex behavioural tasks, such as the rSMT, animals have to integrate reward-related information from multiple sources to guide behaviour. Additionally, animals retain a representation of the outcome of the previous trial that exerts considerable influence over subsequent choices [21,74] and behaviour on such tasks, remains goal-directed, even after extensive training [84]. D 4 receptor activity has been suggested to contribute to maintaining homeostatic PFC activity levels [87,47], theoretically stabilizing representations of reward [22].…”