Effects of Alprazolam on Driving Ability, Memory Functioning and Psychomotor Performance A Randomized, Placebo-controlled Study

Verster, Joris C.

doi:10.1016/s0893-133x(02)00310-x

Cited by 110 publications

(107 citation statements)

References 41 publications

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“…One of the most common experimental tools in intoxicated driving research is the driving simulator, and many studies to date have employed driving simulators to assess the effects of various abused substances and prescribed medications, as well as the effects of normal aging, sleep deprivation, and other adverse conditions on driving and driving related skills (Linnoila and Mattila, 1973;Rimm et al, 1982;Deery and Fildes, 1999;Arnedt et al, 2001;Verster et al, 2002). We have previously demonstrated the validity of a similar, simulated driving environment to evaluate performance measures in sober and alcohol-intoxicated subjects compared directly to real on-road driving (McGinty et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Alcohol Intoxication Effects on Simulated Driving: Exploring Alcohol-Dose Effects on Brain Activation Using Functional MRI

Calhoun

Pekar

Pearlson

2004

Neuropsychopharmacol

172

143

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Driving while intoxicated is a major public health problem. We investigated impaired driving using a simulated driving skill game that presents an 'in-car' view of a road and a readout of speed. We explored brain activation and behavioral alterations from baseline at two blood alcohol concentrations (BACs). Participants received single-blind individualized doses of beverage alcohol designed to produce blood alcohol content (BAC) of 0.04 and 0.08 or placebo. Scanning occurred on a 1.5 Tesla Philips MRI scanner after training to asymptote performance. Analysis was performed using independent component analysis (ICA) to isolate systematically nonoverlapping 'networks' and their time courses. Imaging results revealed seven separate driving-related brain networks with different time courses. Several significant findings were observed for the imaging data. First, dose-dependent functional magnetic resonance imaging (fMRI) changes were revealed in orbitofrontal (OF) and motor (but not cerebellar) regions; visual and medial frontal regions were unaffected. Second, cerebellar regions were significantly associated with driving behavior in a dose-dependent manner. Finally, a global disruptive effect of alcohol on the ICA time courses was observed with highly significant differences in OF and motor regions. Alcohol thus demonstrated some behavioral effects and unique, disruptive, dose-dependent effects on fMRI signal within several brain circuits. The fMRI data also suggest that the deficits observed in alcohol intoxication may be modulated primarily through OF/anterior cingulate, motor and cerebellar regions as opposed to attentional areas in frontoparietal cortex.

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Section: Introductionmentioning

confidence: 99%

Alcohol Intoxication Effects on Simulated Driving: Exploring Alcohol-Dose Effects on Brain Activation Using Functional MRI

Calhoun

Pekar

Pearlson

2004

Neuropsychopharmacol

172

143

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“…The majority of patients who receive BZD therapy continue to take BZD for an extended period of time. This phenomenon is more prevalent in women than men [9], which increases their risk of motoric deficit associated with the prolonged use of BZDs [2,7,9,58]. As shown in Figure 1, mice treated with BZD showed no significant difference in motoric performance compared to vehicle-treated mice during the early stage of BZD injection (day 1 to 8).…”

Section: Discussionmentioning

confidence: 97%

“…While BZD is powerfully effective and largely safe, evidence indicates that the prolonged use of BZDs often creates adverse effects including motoric deficit [2,7,9,58]. Nearly all the disadvantages of BZDs result from long-term use [59], but most mechanistic studies on motor deficit have focused on BZD's acute effect.…”

Section: Discussionmentioning

confidence: 99%

Purkinje-neuron-specific down-regulation of p38 protects motoric function from the repeated use of benzodiazepine

Jung¹,

Metzger²

2013

ABB

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Benzodiazepine (BZD) is the most prescribed CNS depressant in America to treat hyper-excitatory disorders such as anxiety and insomnia. However, the chronic use of BZD often creates adverse effects including psychomotor deficit. In this study, we investigated a novel mechanism by which chronic BZD impedes motoric function in female mice. We used female mice because BZD use is much more prevalent in female than male populations. We tested the hypothesis that the accumulation of p38 (stress-activated protein) in cerebellar Purkinje neurons mediates motoric deficit induced by chronic BZD. To test this hypothesis, we generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38 loxP/loxP mice. p38-knockdown mice and wild-type mice received BZD (lorazepam, 0.5 mg/kg) for 14 days. During this period, they were tested for motoric performance using Rotarod assay in which a quicker fall from rotating rod indicates poorer motoric performance. Cerebellum was then collected to detect p38 in Purkinje neurons and to measure mitochondrial respiration using immunohistochemistry and real-time XF respirometry, respectively. Compared to vehicletreated mice, BZD-treated mice showed poorer motoric performance, a higher number of Purkinje neurons containing p38, and lower mitochondrial respiration. These effects of BZD were much smaller in p38-knockdown mice. These results suggest that the excessive accumulation of p38 in cerebellar Purkinje neurons contributes to motoric deficit associated with chronic BZD. They also suggest that Purkinje neuronal p38 mediates BZD-induced mitochondrial respiratory inhibition in cerebellum. Our findings may provide a new mechanistic insight into chronic BZD-induced motoric deficit.

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“…Alprazolam Fire eksperimentelle studier oppfylte kriteriene til "trafikkrelevante" tester og ble lagt til grunn for fastsettelse av straffeutmålingsgrenser (33,(84)(85)(86). Kjøreferdigheter er studert ved testing i normaltrafikk, i kjøresimulator samt etter måling av SDLP ved bruk av alprazolam.…”

Section: Eksperimentelle Studierunclassified

Revisjon av faste grenser for rusmidler i trafikken

Strand¹,

Innerdal²,

Mathisrud³

et al. 2016

Tidsskriftet

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Effects of Alprazolam on Driving Ability, Memory Functioning and Psychomotor Performance A Randomized, Placebo-controlled Study

Cited by 110 publications

References 41 publications

Alcohol Intoxication Effects on Simulated Driving: Exploring Alcohol-Dose Effects on Brain Activation Using Functional MRI

Alcohol Intoxication Effects on Simulated Driving: Exploring Alcohol-Dose Effects on Brain Activation Using Functional MRI

Purkinje-neuron-specific down-regulation of p38 protects motoric function from the repeated use of benzodiazepine

Revisjon av faste grenser for rusmidler i trafikken

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