Pandemic lockdowns: who feels coerced and why? - a study on perceived coercion, perceived pressures and procedural justice during the UK COVID-19 lockdowns.

BACKGROUND: This study examined perceptions of coercion, pressures and procedural injustice and how such perceptions influenced psychological well-being in those who experienced a UK COVID-19 lockdown, with a view to preparing for the possibility of future lockdowns. METHODS: 40 individuals categorised as perceiving the lockdown(s) as either highly or lowly coercive took part in one of six asynchronous virtual focus groups (AVFGs). RESULTS: Using thematic analysis, the following key themes were identified in participants' discussions: (1) Choice, control and freedom; (2) threats; (3) fairness; (4) circumstantial factors; and (5) psychological factors. CONCLUSIONS: As the first qualitative study to investigate the psychological construct of perceived coercion in relation to COVID-19 lockdowns, its findings suggest that the extent to which individuals perceived pandemic-related lockdowns as coercive may have been linked to their acceptance of restrictions. Preparing for future pandemics should include consideration of perceptions of coercion and efforts to combat this, particularly in relation to differences in equity, in addition to clarity of public health messaging and public engagement.

The effects of paranoia and dopamine on perception of cohesion and conspiracy: a pre-registered, double-blind, placebo-controlled experiment.

Paranoia is a common symptom of psychotic disorders but is also present on a spectrum of severity in the general population. Although paranoia is associated with an increased tendency to perceive cohesion and conspiracy within groups, the mechanistic basis of this variation remains unclear. One potential avenue involves the brain's dopaminergic system, which is known to be altered in psychosis. In this study, we used large-N online samples to establish the association between trait paranoia and perceptions of cohesion and conspiracy. We further evaluated the role of dopamine on perceptions of cohesion and conspiracy using a double-blind, placebo-controlled laboratory experiment where participants received levodopa or a placebo control. Our results were mixed: group perceptions and perceptions of cohesion were higher among more paranoid individuals but were not altered under dopamine administration. We outline the potential reasons for these discrepancies and the broader implications for understanding paranoia in terms of dopamine dysregulation.

Nitrous oxide may interfere with the reconsolidation of drinking memories in hazardous drinkers in a prediction-error-dependent manner.

Weakening drinking-related reward memories by blocking their reconsolidation is a potential novel strategy for treating alcohol use disorders. However, few viable pharmacological options exist for reconsolidation interference in humans. We therefore examined whether the NMDA receptor antagonising gas, Nitrous Oxide (N2O) could reduce drinking by preventing the post-retrieval restabilisation of alcohol memories in a group of hazardous drinkers. Critically, we focussed on whether prediction error (PE; a key determinant of reconsolidation) was experienced at retrieval. Sixty hazardous drinkers were randomised to one of three groups that retrieved alcohol memories either with negative PE (Retrieval + PE), no PE (Retrieval no PE) or non-alcohol memory retrieval with PE (No-retrieval +PE). All participants then inhaled 50% N2O for 30 min. The primary outcome was change in beer consumption and alcohol cue-driven urge to drink from the week preceding manipulation (baseline) to the week following manipulation (test). The manipulation did not affect drinking following the intended retrieval+/- PE conditions However, a manipulation check, using a measure of subjective surprise, revealed that the group-level manipulation did not achieve the intended differences in PE at retrieval. Assessment of outcomes according to whether alcohol-relevant PE was actually experienced at retrieval, showed N2O produced reductions in drinking in a retrieval and PE-dependent fashion. These preliminary findings highlight the importance of directly testing assumptions about memory reactivation procedures in reconsolidation research and suggest that N2O should be further investigated as a potential reconsolidation-blocking agent.

Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma.

BACKGROUND: Post-traumatic stress disorder (PTSD) involves maladaptive long-term memory formation which underlies involuntary intrusive thoughts about the trauma. Preventing the development of such maladaptive memory is a key aim in preventing the development of PTSD. We examined whether the N-methyl d-aspartate receptor (NMDAR) antagonist gas nitrous oxide (N2O) could reduce the frequency of intrusive memories by inhibiting NMDAR-dependent memory consolidation in a laboratory analogue of psychological trauma. METHOD: Participants were randomized to inhale N2O (N = 25) or medical air (N = 25) after viewing a negatively valenced emotional film clip ('trauma film'). Participants subsequently completed a daily diary assessing frequency of intrusive thoughts relating to the film clip. A week later, participants completed an explicit memory recall task related to the film. RESULTS: Post-encoding N2O sped the reduction in intrusive memory frequency, with a significant reduction by the next day in the N2O group compared to 4 days later in the air group. N2O also interacted with post-film dissociation, producing increased intrusion frequency in those who were highly dissociated at baseline. Sleep length and quality the night after viewing the film did not differ between the groups. CONCLUSION: N2O speeds the reduction of intrusive analogue trauma memory in a time-dependent manner, consistent with sleep-dependent long-term consolidation disruption. Further research with this drug is warranted to determine its potential to inoculate against enduring effects of psychological trauma; however, caution is also urged in dissociated individuals where N2O may aggravate PTSD-like symptomatology.

Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation.

The transient period of memory instability that can be triggered when memories are retrieved under certain conditions offers an opportunity to modify the maladaptive memories at the heart of substance use disorders (SUDs). However, very well-learned memories (such as those in excessive drinking and alcohol use disorders) are resistant to destabilisation when retrieved or may not destabilise at all. Memory retrieval and intervention procedures that reliably destabilise and update maladaptive motivational memories may help to improve the long-term treatment of SUDs. In 59 hazardous drinkers, we tested a novel retrieval procedure for destabilising well-learned cue-drinking memory networks that maximises prediction error (PE) via guided expectancy violation during retrieval of these memories. This was compared with a retrieval procedure without PE and no-retrieval controls. We subsequently counterconditioned alcohol cues with disgusting tastes and images in all groups and assessed responding to alcohol stimuli 1 week later. Counterconditioning following PE retrieval produced generalised reductions in oculomotor attentional bias, explicit valuation and outcome expectancies in response to alcohol cues 1 week after intervention, evidence of updating of distributed motivational drinking memory networks. These findings demonstrate that well-learned cue-drinking memories can be destabilised and that learning history need not constrain memory destabilisation if PE is maximised at retrieval. Broad rewriting of diverse aspects of maladaptive memory by counterconditioning is achievable following this procedure. The procedure described may provide a platform for the development of novel memory-modifying interventions for SUDs.

Effects of immediate-release opioid on memory functioning: a randomized-controlled study in patients receiving sustained-release opioids.

BACKGROUND: The effects of opioid medication on cognitive functioning in patients with cancer and non-cancer pain remain unclear. METHOD: In this mechanistic randomized, double-blind, placebo-controlled, cross-over study of patients (n = 20) receiving sustained-release and immediate-release opioid medication as part of their palliative care, we examine memory effects of an additional dose of participants' immediate-release medication (oxycodone or morphine) or placebo. Immediate prose recall and recall of related and unrelated word pairs was assessed pre-and post-drug (placebo or immediate-release opioid). Memory for these stimuli was also tested after a delay on each testing occasion. Finally, performance on an 'interference' word pair task was assessed on the two testing occasions since proactive interference has been posited as a mechanism for acute opioid-induced memory impairment. RESULT: Unlike previous work, we found no evidence of memory impairment for material presented before or after individually tailored, 'breakthrough' doses of immediate-release opioid. Furthermore, immediate-release opioid did not result in increased memory interference. On the other hand, we found enhanced performance on the interference word pair task after immediate-release opioid, possibly indicating lower levels of interference. CONCLUSION: These results suggest that carefully titrated immediate-release doses of opioid drugs may not cause extensive memory impairment as previously reported, and in fact, may improve memory in certain circumstances. Importantly, our findings contrast strikingly with those of a study using the same robust design that showed significant memory impairment. We propose that factors, such as depressive symptoms, education level and sustained-release opioid levels may influence whether impairment is observed following immediate-release opioid treatment.

Journey through the K-hole: phenomenological aspects of ketamine use.

Although recreational use of the dissociative anaesthetic drug ketamine is currently increasing, little is known about the phenomenological aspects of its use. We therefore designed a structured interview to examine initiation experiences, positive and negative effects of ketamine use, and concerns about the drug and its long-term effects. Ninety participants (30 frequent users, 30 infrequent 'recreational' users and 30 ex-users who had abstained from use for at least 3 months) were interviewed and reported drug use was verified by hair sample analysis. The most appealing aspects of ketamine for two-thirds of users were "melting into the surrounding", "visual hallucinations", "out-of-body experiences" and "giggliness". Unappealing effects for half of users were "memory loss" and "decreased sociability". Frequent ketamine users expressed more concerns than other groups about long-term effects on physical health problems, especially K-cramps and cystitis, whereas ex-users were more concerned about mental health problems. Addictive/dependent patterns of behaviour were also a concern: the majority of frequent users reported using the drug without stopping until supplies ran out and the mean increase in dosage in this group was six-fold from initiation to current use. We have identified specific health issues which seem uniquely related to ketamine use. Additionally, the dependence on ketamine frequently reported by users may be a cause for concern as its popularity grows and substance misuse services should be made aware of this when clients present in the future.

Scopolamine induces impairments in the recognition of human facial expressions of anger and disgust.

RATIONALE: Recent psychopharmacological studies lend support to the notion of partially dissociable neuronal systems dedicated to processing specific emotions. For example, GABA-ergic enhancement after an acute dose of the benzodiazepine, diazepam, produces specific impairments in anger and fear recognition. However, it is unclear if these impairments are a general property of benzodiazepines and other drugs that produce a similar profile of neurocognitive impairment to benzodiazepines, such as the anticholinergic, scopolamine. OBJECTIVE: We investigated the effects of scopolamine and the benzodiazepine, lorazepam, on emotion-recognition accuracy. METHODS: A double-blind independent group design was used with 48 healthy volunteers to compare the effects of scopolamine and lorazepam with an inactive placebo on a commonly used emotion-recognition task. Control measures included an episodic memory task and subjective mood ratings. RESULTS: Anger and disgust recognition accuracy was impaired after scopolamine. In contrast, lorazepam produced no impairment in emotion-recognition despite producing similar levels of sedation and anterograde amnesia to scopolamine. CONCLUSIONS: Scopolamine-induced cholinergic hypofunction selectively impaired the recognition accuracy of disgust and anger facial expressions. The effects of scopolamine on emotion-recognition are similar to those found in Huntington's disease patients. Furthermore, the impairments in anger and fear recognition previously observed with diazepam do not appear to be a general property of benzodiazepines. This suggests that alterations in emotional processing involving changes in the ability to recognize threat-related emotions (particularly, fear and anger) may not be a principal mechanism underlying anxiolysis or paradoxical aggression seen with benzodiazepines.

Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition.

Non-NMDA glutamate receptor subunits of the AMPA-preferring subfamily combine to form ion channels with heterogeneous functional properties. We have investigated the effects of RNA editing at the Q/R site, splice variation of the "flip/flop" cassette, and multimeric subunit assembly on the single-channel conductance and kinetic properties of the recombinant AMPA receptors formed from GluR2 and GluR4 expressed in HEK 293 cells. We found that AMPA receptor single-channel conductance was dependent on the Q/R site editing state of the subunits comprising the channel. Calcium-permeable (unedited) channels had resolvable single-channel events with main conductance states of 7-8 pS, whereas fully edited GluR2 channels had very low conductances of approximately 300 fS (estimated from noise analysis). Additionally, the flip splice variant of GluR4 conferred agonist-dependent conductance properties reminiscent of those found for a subset of AMPA receptors in cultured cerebellar granule cells. These results provide a description of the single-channel properties of certain recombinant AMPA receptors and suggest that the single-channel conductance may be determined by the expression of edited GluR2 subunits in neurons.

Intracellular spermine confers rectification on rat calcium-permeable AMPA and kainate receptors.

1. Whole-cell recordings were made from cerebellar granule cells cultured in high-K+ medium to induce expression of Ca(2+)-permeable AMPA receptors. Current-voltage (I-V) plots of agonist-evoked responses showed varying degrees of inward rectification, but became linear within 5-10 min. 2. Recombinant Ca(2+)-permeable kainate receptors, composed of GluR6(Q)/KA-2 subunits, exhibited rectifying whole-cell I-V plots that became linear in outside-out patches. 3. Loss of rectification in granule cells was prevented by including 100 microM spermine in the pipette; the degree of rectification was then correlated with Ca2+ permeability. 4. Spermine also prevented loss of rectification in patches containing GluR6(Q)/KA-2 receptors (IC50, 1.7 microM). 5. We suggest that spermine, or a similar cellular constituent, may act as a cytoplasmic factor conferring inward rectification on Ca(2+)-permeable non-NMDA receptors, and that 'washout' of this factor underlies the observed loss of rectification.