Dexamphetamine effects on prepulse inhibition (PPI) and startle in healthy volunteers

Chitty, Kate M.; Albrecht, Matthew A.; Graham, Kyran T.; Kerr, C. Lance; Lee, Joseph W.Y.; Iyyalol, Rajan; Martin‐Iverson, Mathew T.

doi:10.1007/s00213-013-3395-z

Cited by 9 publications

(11 citation statements)

References 48 publications

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“…In line with this, our recent experiments with mephedrone, nor-mephedrone, and MDPV showed comparable weak or negative effects on PPI in rats (unpublished observations Horsley et al and Sichova et al). Interestingly amphetamine, which is approximately 10 times more potent in disrupting PPI in rodents, in humans also failed to have disruptive effect on PPI ( 41 ). However, this might be related to the fact that it was used in much lower dose (0.45 mg/kg) in humans compared with rodents (typically 1–4 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats

et al. 2017

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Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused our research on pharmacokinetics, and on a detailed evaluation of temporal effects of methylone and its metabolite nor-methylone on behavior and body temperature in rats. Methylone [5, 10, 20, and 40 mg/kg subcutaneously (s.c.)] and nor-methylone (10 mg/kg s.c.) were used in adolescent male Wistar rats across three behavioral/physiological procedures and in two temporal windows from administration (15 and 60 min) in order to test: locomotor effects in the open field, sensorimotor gating in the test of prepulse inhibition (PPI), and effects on rectal temperature in individually and group-housed rats. Serum and brain pharmacokinetics after 10 mg/kg s.c. over 8 h were analyzed using liquid chromatography mass spectrometry. Serum and brain levels of methylone and nor-methylone peaked at 30 min after administration, both drugs readily penetrated the brain with serum: brain ratio 1:7.97. Methylone dose-dependently increased overall locomotion. It also decrease the amount of time spent in the center of open field arena in dose 20 mg/kg and additionally this dose induced stereotyped circling around the arena walls. The maximum of effects corresponded to the peak of its brain concentrations. Nor-methylone had approximately the same behavioral potency. Methylone also has weak potency to disturb PPI. Behavioral testing was not performed with 40 mg/kg, because it was surprisingly lethal to some animals. Methylone 10 and 20 mg/kg s.c. induced hyperthermic reaction which was more pronounced in group-housed condition relative to individually housed rats. To conclude, methylone increased exploration and/or decreased anxiety in the open field arena and with nor-methylone had short duration of action with effects typical for mixed indirect dopamine–serotonin agonists such as 3,4-metyhlenedioxymethamphetamine (MDMA) or amphetamine. Given the fact that the toxicity was even higher than the known for MDMA and that it can cause hyperthermia it possess a threat to users with the risk for serotonin syndrome especially when used in crowded conditions.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats

et al. 2017

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“…In one session, participants were given a single dose of dexamphetamine sulfate (Sigma Pharmaceuticals Pty Ltd., Victoria, Australia) at 0.45 mg/kg (to the nearest 2.5 mg) in oral capsule form. This research group has demonstrated that administration of this dose of dexamphetamine induces changes in multiple behavioral (Albrecht et al, ; Chitty et al, ) and physiological markers (Albrecht, Price, Lee, Iyyalol, & Martin‐Iverson, ; Albrecht et al, ). The mean weight and dose of participants are given in Table .…”

Section: Methodsmentioning

confidence: 99%

Setting the beat of an internal clock: Effects of dexamphetamine on different interval ranges of temporal processing in healthy volunteers

2019

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Drug studies are powerful models to investigate the neuropharmacological mechanisms underlying temporal processing in humans. This study administered dexamphetamine to 24 healthy volunteers to investigate time perception at different time scales, along with contributions from working memory. Healthy volunteers were administered 0.45 mg/kg dexamphetamine or placebo in a doubleblind, crossover, placebo-controlled design. Time perception was assessed using three experimental tasks: a time-discrimination task, which asked participants to determine whether a comparison interval (1200 AE 0, 50, 100, 150, 200 ms) was shorter or longer than a standard interval (1200 ms); a retrospective time estimation task, which required participants to verbally estimate time intervals (10, 30, 60, 90 and 120 s) retrospectively; and a prospective time-production task, where participants were required to prospectively monitor the passing of time (10, 30, 60, 90 and 120 s). Working memory was assessed with the backwards digit span. On the discrimination task, there was a change in the proportion of long-to-short responses and reaction times in the dexamphetamine condition (but no association with working memory), consistent with an increase in the speed of an internal pacemaker, and an overestimation of durations in the timing of shorter intervals. There was an interaction between dexamphetamine, working memory, and performance on the estimation and production tasks, whereby increasing digit span scores were associated with decreasing interval estimates and increased produced intervals in the placebo condition, but were associated with increased interval estimates and decreased produced intervals after dexamphetamine administration. These findings indicate that the dexamphetamine-induced increase in the speed of the internal pacemaker was modulated by the basal working memory capacity of each participant. These findings in healthy humans have important implications for the role of dopamine, and its contributions to timing deficits, in models of psychiatric disorders.

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“…More details on the model are provided in Supporting Information and the models are an extension of those used in previous publications [Chitty et al, ; Lam et al, ]. The prior for the overall effect of dexamphetamine was described by a normal distribution centered on 0 with a standard deviation equal to 1, i.e., it was anticipated that regardless of the direction of the effect of dexamphetamine, the effect size was most likely to be well within 1–2 standard deviations of the difference scores.…”

Section: Methodsmentioning

confidence: 99%

The effects of dexamphetamine on the resting‐state electroencephalogram and functional connectivity

Albrecht

Roberts

Price

et al. 2015

Human Brain Mapping

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The catecholamines-dopamine and noradrenaline-play important roles in directing and guiding behavior. Disorders of these systems, particularly within the dopamine system, are associated with several severe and chronically disabling psychiatric and neurological disorders. We used the recently published group independent components analysis (ICA) procedure outlined by Chen et al. (2013) to present the first pharmaco-EEG ICA analysis of the resting-state EEG in healthy participants administered 0.45 mg/kg dexamphetamine. Twenty-eight healthy participants between 18 and 41 were recruited. Bayesian nested-domain models that explicitly account for spatial and functional relationships were used to contrast placebo and dexamphetamine on component spectral power and several connectivity metrics. Dexamphetamine led to reductions across delta, theta, and alpha spectral power bands that were predominantly localized to Frontal and Central regions. Beta 1 and beta 2 power were reduced by dexamphetamine at Frontal ICs, while beta 2 and gamma power was enhanced by dexamphetamine in posterior regions, including the parietal, occipital-temporal, and occipital regions. Power-power coupling under dexamphetamine was similar for both states, resembling the eyes open condition under placebo. However, orthogonalized measures of power coupling and phase coupling did not show the same effect of dexamphetamine as power-power coupling. We discuss the alterations of low- and high-frequency EEG power in response to dexamphetamine within the context of disorders of dopamine regulation, in particular schizophrenia, as well as in the context of a recently hypothesized association between low-frequency power and aspects of anhedonia. Hum Brain Mapp 37:570-588, 2016. © 2015 Wiley Periodicals, Inc.

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Dexamphetamine effects on prepulse inhibition (PPI) and startle in healthy volunteers

Abstract: Results indicate that sex differences exist in motor, but not sensory, components of the startle reflex. Findings also reveal that administration of 0.45 mg/kg dexamphetamine to healthy humans does not mimic PPI effects observed in schizophrenia.

Cited by 9 publications

References 48 publications

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats

Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats

Setting the beat of an internal clock: Effects of dexamphetamine on different interval ranges of temporal processing in healthy volunteers

The effects of dexamphetamine on the resting‐state electroencephalogram and functional connectivity

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