Chronic Exposure to Methamphetamine Disrupts Reinforcement-Based Decision Making in Rats

Groman, Stephanie M.; Rich, Katherine M.; Smith, Nathaniel J.; Lee, Dongsoo; Taylor, Jane R.

doi:10.1038/npp.2017.159

Cited by 50 publications

(59 citation statements)

References 54 publications

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“…We analysed belief updating across three reversal-learning experiments (Fig. 1): an in laboratory pilot of patients and healthy controls, stratified by stable, paranoid personality trait (Experiment 1); four online task variants administered to participants via the Amazon Mechanical Turk (MTurk) marketplace (Experiment 2); and a re-analysis of data from rats on chronic, escalating doses of methamphetamine, a translational model of paranoia (Experiment 3) 32 .…”

Section: Resultsmentioning

confidence: 99%

“…Experiment 3. To translate across species, we performed a new analysis of published data from rats exposed to chronic methamphetamine 32 . Rats chose between three operant chamber noseports with differing probabilities of sucrose reward (70%, 30%, and 10%; Fig.1 d and e).…”

Section: Resultsmentioning

confidence: 99%

“…1e). Rats were tested for 26 within-session reversal blocks (Pre-Rx, n =10 per group), administered saline or methamphetamine according to a 23-day schedule mimicking the escalating doses and frequencies of chronic human methamphetamine users 32 , and tested once per week for four weeks following completion of the drug regimen (Post-Rx; n =10 saline, 7 methamphetamine) 32 . Relative to rats exposed to saline, those rats exposed to methamphetamine exhibited increased win-switch behaviour and perseveration after negative feedback 32 .…”

Section: Resultsmentioning

confidence: 99%

“…Win-switching was the prominent behavioural feature of both paranoid participants and rats exposed to methamphetamine (Table 1, Table 2, 32 ). Collapsed across blocks and task versions, our Experiment 2 data demonstrated a main effect of paranoia group (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We examined the behavioural and computational correlates of paranoia both in-person and in a large online sample, spanning patients and healthy controls with varying degrees of paranoia. We also undertook a pre-clinical replication in rodents exposed chronically to saline or methamphetamine 32 . We predicted that paranoia-related learning differences would be particularly prominent in settings of contextual change.…”

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confidence: 99%

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Expecting the unexpected: the paranoid style of belief updating across species

Reed

Uddenberg

Mathys

et al. 2020

Preprint

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55Paranoia is the belief that harm is intended by others. It may arise from selective pressures to infer and avoid 56 social threats, particularly in ambiguous or changing circumstances. We propose that uncertainty may be 57 sufficient to elicit learning differences in paranoid individuals, without social threat. We used reversal learning 58 behaviour and computational modelling to estimate belief updating across individuals with and without mental 59 illness, online participants, and rats exposed to chronic methamphetamine, an elicitor of paranoia in humans. 60Paranoia is associated with a strong but immutable prior on volatility, accompanied by elevated sensitivity to 61 perceived changes in the task environment. Methamphetamine exposure in rats recapitulates this impaired 62 uncertainty-driven belief updating and rigid anticipation of a volatile environment. Our work provides evidence 63 of fundamental, domain-general learning differences in paranoid individuals. This paradigm enables further 64 assessment of the interplay between uncertainty and belief-updating across individuals and species. 66 67Paranoia & Belief Updating 3 Paranoia is excessive concern that harm will occur due to deliberate actions of others 1 . It manifests along a 68 continuum of increasing severity 2-5 . Fleeting paranoid thoughts prevail in the general population 6 . A survey of 69 over 7,000 individuals found that nearly 20% believed people were against them at times in the past year; 70 approximately 8% felt people had intentionally acted to harm them 4 . At a national level, paranoia may fuel 71 divisive ideological intolerance. Historian Richard Hofstadter famously described catastrophizing, context 72 insensitive political discourse as the 'paranoid style': 73 "The paranoid spokesman sees the fate of conspiracy in apocalyptic terms-he traffics in the birth 74 and death of whole worlds, whole political orders, whole systems of human values. He is always 75 manning the barricades of civilization. He constantly lives at a turning point." 7 76 77 At its most severe, paranoia manifests as rigid beliefs known as delusions of persecution. These delusions 78 occur frequently in psychotic illness, including nearly 90% of first episode patients 8 . However, paranoid beliefs 79 are common across psychiatric and neurologic disorders, such as anxiety 9 , depression 10 , epilepsy 11 , and 80 Alzheimer's disease 12 . Psychostimulants elicit severe paranoid states. Methamphetamine evoked new 81paranoid ideation in nearly half of 274 respondents, particularly after repeated exposure (86%) or escalating 82 dose (68%) 13 . Of those who became paranoid, the majority engaged in evasive defence strategies (hiding or 83 fleeing), but 37% obtained weapons, and 15% attacked others. There is a clear need to better manage 84 paranoia, and to understand and address its broader societal impact. 86Paranoia has thus far defied explanation in mechanistic terms, either at the levels of behaviour or brain 87 function. Obvious links with fear processing and social ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%