Instrumental analysis of ethanol-induced intoxication in human males

Lukas, Scott E.; Mendelson, Jack H.; Benedikt, Richard A.

doi:10.1007/bf00175181

Cited by 54 publications

(15 citation statements)

References 31 publications

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“…increased as the experiment progressed, but the mean PIL decreased (Figure 4). This inverse relationship is similar to the findings of Lukas, Mendelson, and Benedikt (1986), who found that perceived intoxication ratings begin to decline sooner than plasma alcohol levels. Thus, there was no systematic relationship between objective and subjective estimates of intoxication.…”

Section: Methodssupporting

confidence: 88%

Measuring and predicting the effects of alcohol consumption on contrast sensitivity for stationary and moving gratings

Andre

Tyrrell

Leibowitz

et al. 1994

Perception & Psychophysics

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Contrast sensitivity was measured for 12 healthy young males while sober, after ingestion of an alcohol placebo, and after ingestion of alcohol (95% grain alcohol; mean estimated blood alcohol level = .088%). Observations were made for both stationary gratings and gratings that traveled through a circular path and required pursuit eye movements. The significant alcohol-related reduction in contrast sensitivity was 2.6 times greater for moving (.29-10g-unit reduction) than for stationary gratings (.I1-10g-unit reduction). The loss in contrast sensitivity for the moving gratings of high spatial frequency (12 cpd) was particularly severe (.37 log unit). Estimated blood alcohol level was correlated with the loss in contrast sensitivity for moving gratings (r = .61), but not with the loss for stationary gratings. Estimated blood alcohol level was strongly correlated with the difference between the loss in contrast sensitivity to moving and stationary gratings (r = .75). These results are consistent with reports that alcohol consumption degrades the ability to make pursuit eye movements. Subjects' perceived intoxication level was not a reliable predictor of any index of visual performance. 261Although a sizable literature addresses the question of whether alcohol affects visual performance (e.g., Adams

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Section: Methodssupporting

confidence: 88%

Measuring and predicting the effects of alcohol consumption on contrast sensitivity for stationary and moving gratings

Andre

Tyrrell

Leibowitz

et al. 1994

Perception & Psychophysics

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“…A shorter duration of exposure at higher toluene concentrations resulting in increased ICSS facilitation may be a result of conducting ICSS testing while drug levels are rapidly rising in the CNS. This interpretation is consistent with the observation in humans that the euphoric/hedonic effects of amphetamine and ethanol are most prominent when the drug plasma levels are on the ascending portion of the pharmacokinetic curve (Lukas et al 1986a; Lukas et al 1986b; Brauer et al 1996). …”

Section: Discussionsupporting

confidence: 91%

Negative allosteric modulation of GABAA receptors inhibits facilitation of brain stimulation reward by drugs of abuse in C57BL6/J mice

2015

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Rationale There is an emerging body of evidence that implicates a crucial role of γ-aminobutyric acid subtype A (GABAA) receptors in modulating the rewarding effects of a number of abused drugs. Modulation of GABAA receptors may therefore represent a novel drug-class independent mechanism for the development of abuse treatment pharmacotherapeutics. Objectives We tested the hypothesis that the GABAA receptor benzodiazepine-site (BDZ) negative modulator Ro15-4513 would reduce the reward-related effects of three pharmacologically dissimilar drugs; toluene vapor, d-methamphetamine and diazepam using intracranial self-stimulation (ICSS) in mice. We also examined whether Ro15-4513 attenuated dopamine release produced by d-methamphetamine in an in vivo microdialysis procedure. Results Ro15-4513 abolished ICSS reward facilitation produced by all three abused drugs at Ro15-4513 doses which had no effect on ICSS when administered alone. In contrast, the BDZ antagonist flumazenil only attenuated the ICSS-facilitating effects of diazepam. Administration of the same dose of Ro15-4513 which abolished drug-facilitated ICSS produced a 58% decrease in d-methamphetamine stimulated dopamine in the nucleus accumbens of mice relative to d-methamphetamine alone. Conclusions These results demonstrate that negative modulation of GABAA receptors can produce profound reductions in reward-related effects on a diverse group of drugs that activate the mesolimbic reward pathway through different mechanisms. These data suggest that pharmacological modulation of GABAA receptors may represent a viable pathway for the development of drug abuse pharmacotherapies.

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“…In the first phase of the study, subjects used an instrumental joystick device (Lukas et al, 1986a(Lukas et al, , 1986b. They were instructed to pull the joystick backward whenever they felt a cocaine effect and release it when the effect was gone.…”

Section: Subjective Measuresmentioning

confidence: 99%

Benztropine pretreatment does not affect responses to acute cocaine administration in human volunteers

Penetar

Looby

Su³

et al. 2006

Hum. Psychopharmacol. Clin. Exp.

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Benztropine (Cogentin ) was evaluated for its ability to block cocaine's physiological and subjective effects in humans. In healthy, recreational users of cocaine, placebo, or benztropine (1, 2, and 4 mg orally) was given 2 hr before subjects self-administered 0.9 mg/kg of cocaine intranasally. Measurements were made for 2 hr following cocaine administration, and plasma cocaine and cocaine metabolites were assayed. Cocaine produced typical increases in heart rate and alterations in self-reports measured by visual analog scales (VAS). Benztropine alone did not produce changes on any of these measures. Responses to cocaine with and without benztropine pretreatment were similar: benztropine did not change cocaine's effects. This study of one of the tropane-ring analogs that is approved for human use suggests this compound does not alter cocaine-induced effects, but just as importantly, does not produce any adverse behavioral or physiological effects. The exact therapeutic application of benztropine as a possible adjunct treatment for cocaine abuse in humans require further exploration.

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Instrumental analysis of ethanol-induced intoxication in human males

Cited by 54 publications

References 31 publications

Measuring and predicting the effects of alcohol consumption on contrast sensitivity for stationary and moving gratings

Measuring and predicting the effects of alcohol consumption on contrast sensitivity for stationary and moving gratings

Negative allosteric modulation of GABAA receptors inhibits facilitation of brain stimulation reward by drugs of abuse in C57BL6/J mice

Benztropine pretreatment does not affect responses to acute cocaine administration in human volunteers

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