Phencyclidine Disrupts Neural Coordination and Cognitive Control by Dysregulating Translation.

Background: Phencyclidine (PCP) causes psychosis, is abused with increasing frequency, and was extensively used in antipsychotic drug discovery. PCP discoordinates hippocampal ensemble action potential discharge and impairs cognitive control in rats, but how this uncompetitive NMDA receptor (NMDAR) antagonist impairs cognition remains unknown. Methods: The effects of PCP were investigated on hippocampal CA1 ensemble action potential discharge in vivo in urethane-anesthetized rats and during awake behavior in mice, on synaptic responses in ex vivo mouse hippocampus slices, in mice on a hippocampus-dependent active place avoidance task that requires cognitive control, and on activating the molecular machinery of translation in acute hippocampus slices. Mechanistic causality was assessed by comparing the PCP effects with the effects of inhibitors of protein synthesis, group I metabotropic glutamate receptors (mGluR1/5), and subunit-selective NMDARs. Results: Consistent with ionotropic actions, PCP discoordinated CA1 ensemble action potential discharge. PCP caused hyperactivity and impaired active place avoidance, despite the rodents having learned the task before PCP administration. Consistent with metabotropic actions, PCP exaggerated protein synthesis-dependent DHPG-induced mGluR1/5-stimulated long-term synaptic depression. Pretreatment with anisomycin or the mGluR1/5 antagonist MPEP, both of which repress translation, prevented PCP-induced discoordination and the cognitive and sensorimotor impairments. PCP as well as the NR2A-containing NMDAR antagonist NVP-AAM077 unbalanced translation that engages the Akt, mTOR (mechanistic target of rapamycin), and 4EBP1 translation machinery and increased protein synthesis, whereas the NR2B-containing antagonist Ro25-6981 did not. Conclusions: PCP dysregulates translation, acting through NR2A-containing NMDAR subtypes, recruiting mGluR1/5 signaling pathways, and leading to neural discoordination that is central to the cognitive and sensorimotor impairments.

Do losses disguised as wins create a "sweet spot" for win overestimates in multiline slots play?

Multiline slots are popular electronic gaming machines. Research suggests that particular outcomes on these games, namely losses disguised as a wins or LDWs, may make these games particularly alluring to gamblers. LDWs occur when one wins less than they wager, but the machine celebrates these net losses with flashing lines and winning sounds (e.g., bet a dollar, win back a dime). Players are known to somatically, psychologically, and behaviourlly miscategorize LDWs as wins rather than losses. Furthermore, LDWs lead players to overestimate how many times they thought they won during a playing session - leading to what is known as the LDW-triggered win-overestimation effect. In this paper, we analyzed experienced players' win-overestimates from 13 studies after playing slots with different LDW percentages. The combined data showed an inverted U-shaped function for win-overestimates. There appears to be a "sweet spot" for the LDW-triggered win-overestimation effect; wherein, a moderate number of LDWs maximizes this effect, but a high number of LDWs decreases the effect. In Study 2, we confirmed with 132 experienced gamblers that there appears to be maximal win overestimates at around 19.6% LDWs. We conjecture that a high number of LDWs may lead players to see a disconnection between the running total on the machine going down and the number of "wins", leading to more accurate win estimates. This inverted "U" effect for win-overestimates parallels previous research showing that gamblers continue to play for longer during a losing streak following a playing session with a moderate (versus low or high) number of LDWs. LDW-triggered win-overestimates may contribute to the allure of multiline slots -games that cause significant problems for a subset of gamblers.

Reward reactivity and dark flow in slot-machine gambling: "Light" and "dark" routes to enjoyment.

BACKGROUND AND AIMS: Slot machines are a very popular form of gambling. In this study, we look at two different routes to enjoying slots play. One route involves the degree to which players react to rewards. The other route involves what we call dark flow - a pleasurable, but maladaptive state where players become completely engrossed in slots play, providing an escape from the depressing thoughts that characterize their everyday lives. METHODS: One hundred and twenty-nine high-frequency slots players were tested on slot-machine simulators set up in the lobby of a casino. We measured reward reactivity using post-reinforcement pauses (PRPs) and the force with which players pressed the spin button following different slot-machine outcomes. For each player, we calculated the slopes of PRPs and force as a function of credit gains. We also assessed players' slots game enjoyment and their experience of dark flow, depression, and problem gambling. RESULTS: Both the PRP and the force measures of reward reactivity were significantly correlated with players' enjoyment of the slots session, but neither measure was correlated with either problem gambling or depression. Ratings of dark flow were strongly correlated with slots enjoyment (which accounted for far more positive affect variance than the reward reactivity measures) and were correlated with both problem gambling scores and depression. DISCUSSION AND CONCLUSIONS: Our results suggest that of these two routes to enjoying slot-machine play, the dark flow route is especially problematic. We contend that the dark flow state may be enjoyable because it provides escape from the negative thoughts linked to depression.

Mindfulness problems and depression symptoms in everyday life predict dark flow during slots play: Implications for gambling as a form of escape.

Slot machine players refer to a state of absorption that researchers have labeled dark flow. Players become completely occupied by the game and forget everything else (leading to "dark" consequences such as spending more money than intended). We propose that players who experience dark flow have difficulty staying on task in everyday life, but, the reinforcing sights and sounds of slot machines rein in these otherwise wandering minds and induce these flow-like states. We assessed 129 gamblers for mindfulness problems (using the Mindful Attention Awareness Scale), gambling problems (using the Problem Gambling Severity Index), and depressive symptoms (using the Depression Anxiety and Stress Scale). Participants played a slot machine simulator and were periodically interrupted with thought probes to assess whether they were thinking about the game or about something else. After playing, we retrospectively assessed dark flow and positive affect during play. Our key results were that mindfulness problems outside of the gambling context were positively correlated with depression, problem gambling status, and most importantly, dark flow within the gambling context. Dark flow was positively correlated with positive affect during play and the combination of dark flow and depression predicted gambling problems. The picture that emerges is that individuals with mindfulness problems in everyday life find their attention locked in by slot machines inducing dark flow, which in turn leads to a state of positive affect. For depressed players especially, this state may be enjoyable because it provides an escape from the negative mentation linked to depression that characterizes the everyday lives of these troubled players. (PsycINFO Database Record (c) 2019 APA, all rights reserved).