Mechanisms of drug-induced driving impairment: a dimensional approach

Abstract

Road trac accidents are largely determined by human errors in information processing and attention. Attentional functions constitute a vulnerable link in the human information processing chain. Three distinct attentional brain mechanisms are described that are considered to be involved in the supply of nervous energy for information processing. Arousal, phasic physiological responses to novel stimuli; Activation, tonic physiological readiness to respond; and Eort, the voluntarily exerted coordination between arousal and activation. These energy supply systems are mainly driven by noradrenergic, dopaminergic and cholinergic neurotransmission, respectively. Furthermore, they are aected by a behavioural inhibition system controlled by serotonin. The histamine neurotransmitter system is also associated with behavioural activation, whereas the neurotransmitter GABA has an inhibitory in¯uence on the noradrenergic, dopaminergic and cholinergic systems. It is argued that the eects of drugs on driving can be predicted in terms of their eects on these neurochemical systems. Drugs that decrease noradrenaline-, acetylcholine-, dopamine-and histamine-neurotransmitter turn-over impair dierent facets of attention. GABAergic drugs are sedative, while serotonergic drugs seem to in¯uence attention in a more subtle manner. Any pharmacological intervention on one or more of these systems via medicinal or other psychoactive drugs, can alter, and often impair, driving performance. The assessment of behavioural, psychophysiological and pharmacological markers of the attentional systems during driving performance may provide clues for the answer to the question how, rather than if, drugs have an in¯uence on driving performance. #

Human Cognition Assessment in Drug Research

“…The classification of attentional functions, i.e. arousal, activation, effort and behavioural inhibition in terms of the modulatory effects of noradrenergic, dopaminergic, cholinergic and serotonergic neurotransmitters systems within their major projection targets, rather than their classification in terms of regional brain anatomy as in classical neuropsychology, provides strong clues for the prediction of drug effects on human behaviour [24].…”

Human Cognition Assessment in Drug Research

“…The classification of attentional functions, i.e. arousal, activation, effort and behavioural inhibition in terms of the modulatory effects of noradrenergic, dopaminergic, cholinergic and serotonergic neurotransmitters systems within their major projection targets, rather than their classification in terms of regional brain anatomy as in classical neuropsychology, provides strong clues for the prediction of drug effects on human behaviour [24].…”

Do Zopiclone, Zolpidem and Flunitrazepam have Residual Effects on Simulated Task of Collision Anticipation?

“…On the other hand, in an actual over-the-road driving test, 7.5 mg of zopiclone caused residual effects among insomniac subjects after two nights of treatment (Volkerts et al, 1984), increasing variability of vehicle's lateral position. The day after a single dose taken by a small sample of healthy subjects (n = 9), this molecule did not lead to any modification in response time for braking (Harrison et al, 1985), whereas with a larger sample, in early morning, the average variance in the lateral position of the vehicle increased (Vermeeren et al, 1998;Bocca et al, 1999;Vermeeren et al, 2002).…”

“…Psychotropic drugs (alcohol, narcotics, medication) act on the central nervous system and alter its functions. This alteration causes behavioural modifications which can lead to an increase in driving risks (Brookhuis, 1998;Riedel et al, 1998;Maes et al, 1999;Menzin et al, 2001).…”

Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man

“…Different neuroanatomical, neurochemical and behavioural functions characterize its multidimensional nature. Stimulusmediated arousal, tonic readiness to respond, voluntary effort and behavioural inhibition have been outlined as functions controlling wakefulness, distinctly mediated by noradrenergic, dopaminergic, cholinergic and serotonergic neurochemical modulation (Robbins and Everitt, 1995;Riedel et al, 1998;Robbins, 1997). Noradrenaline (NA) is mainly involved in rapid but transient changes in cortical arousal in response to outside stimuli, whereas dopamine (DA) and acetylcholine (Ach) are thought to be primarily associated with an internally driven energetic state, which varies more slowly and is not readily modulated by external stimulation (McGuiness and Pribram, 1980;Robbins, 1984).…”

Human Cognition Assessment in Drug Research

“…The classification of attentional functions, i.e. arousal, activation, effort and behavioural inhibition in terms of the modulatory effects of noradrenergic, dopaminergic, cholinergic and serotonergic neurotransmitters systems within their major projection targets, rather than their classification in terms of regional brain anatomy as in classical neuropsychology, provides strong clues for the prediction of drug effects on human behaviour [24].…”

Do Zopiclone, Zolpidem and Flunitrazepam have Residual Effects on Simulated Task of Collision Anticipation?

“…On the other hand, in an actual over-the-road driving test, 7.5 mg of zopiclone caused residual effects among insomniac subjects after two nights of treatment (Volkerts et al, 1984), increasing variability of vehicle's lateral position. The day after a single dose taken by a small sample of healthy subjects (n = 9), this molecule did not lead to any modification in response time for braking (Harrison et al, 1985), whereas with a larger sample, in early morning, the average variance in the lateral position of the vehicle increased (Vermeeren et al, 1998;Bocca et al, 1999;Vermeeren et al, 2002).…”

“…Psychotropic drugs (alcohol, narcotics, medication) act on the central nervous system and alter its functions. This alteration causes behavioural modifications which can lead to an increase in driving risks (Brookhuis, 1998;Riedel et al, 1998;Maes et al, 1999;Menzin et al, 2001).…”

Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man

“…Different neuroanatomical, neurochemical and behavioural functions characterize its multidimensional nature. Stimulusmediated arousal, tonic readiness to respond, voluntary effort and behavioural inhibition have been outlined as functions controlling wakefulness, distinctly mediated by noradrenergic, dopaminergic, cholinergic and serotonergic neurochemical modulation (Robbins and Everitt, 1995;Riedel et al, 1998;Robbins, 1997). Noradrenaline (NA) is mainly involved in rapid but transient changes in cortical arousal in response to outside stimuli, whereas dopamine (DA) and acetylcholine (Ach) are thought to be primarily associated with an internally driven energetic state, which varies more slowly and is not readily modulated by external stimulation (McGuiness and Pribram, 1980;Robbins, 1984).…”

Human Cognition Assessment in Drug Research

“…The classification of attentional functions, i.e. arousal, activation, effort and behavioural inhibition in terms of the modulatory effects of noradrenergic, dopaminergic, cholinergic and serotonergic neurotransmitters systems within their major projection targets, rather than their classification in terms of regional brain anatomy as in classical neuropsychology, provides strong clues for the prediction of drug effects on human behaviour [24].…”

Do Zopiclone, Zolpidem and Flunitrazepam have Residual Effects on Simulated Task of Collision Anticipation?

“…On the other hand, in an actual over-the-road driving test, 7.5 mg of zopiclone caused residual effects among insomniac subjects after two nights of treatment (Volkerts et al, 1984), increasing variability of vehicle's lateral position. The day after a single dose taken by a small sample of healthy subjects (n = 9), this molecule did not lead to any modification in response time for braking (Harrison et al, 1985), whereas with a larger sample, in early morning, the average variance in the lateral position of the vehicle increased (Vermeeren et al, 1998;Bocca et al, 1999;Vermeeren et al, 2002).…”

“…Psychotropic drugs (alcohol, narcotics, medication) act on the central nervous system and alter its functions. This alteration causes behavioural modifications which can lead to an increase in driving risks (Brookhuis, 1998;Riedel et al, 1998;Maes et al, 1999;Menzin et al, 2001).…”

Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man

“…Different neuroanatomical, neurochemical and behavioural functions characterize its multidimensional nature. Stimulusmediated arousal, tonic readiness to respond, voluntary effort and behavioural inhibition have been outlined as functions controlling wakefulness, distinctly mediated by noradrenergic, dopaminergic, cholinergic and serotonergic neurochemical modulation (Robbins and Everitt, 1995;Riedel et al, 1998;Robbins, 1997). Noradrenaline (NA) is mainly involved in rapid but transient changes in cortical arousal in response to outside stimuli, whereas dopamine (DA) and acetylcholine (Ach) are thought to be primarily associated with an internally driven energetic state, which varies more slowly and is not readily modulated by external stimulation (McGuiness and Pribram, 1980;Robbins, 1984).…”