Discriminative-Stimulus Effects of Triazolam in Light and Moderate Drinkers

Rush, Craig R.; Kelly, Thomas C.; Fillmore, Mark T.; Hays, Lon R.

doi:10.1097/01.alc.0000062742.29158.6e

Cited by 5 publications

(6 citation statements)

References 27 publications

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“…Peak behavioral effects of 0.25 mg/70 kg triazolam occurred between 1.5 and 2.5 h post-dose, which is consistent with previous reports (e.g., Simpson and Rush 2002; Rush et al 2003). …”

Section: Discussionsupporting

confidence: 91%

Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women

et al. 2011

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Rationale Gender plays a critical role in the effects of drugs and drug abuse liability. Biological factors, including ovarian hormones, may contribute to gender differences in drug abuse. Preclinical and some clinical research suggests that progesterone and its metabolites have activity at the GABAA receptor and may enhance the effect of GABAergic compounds (e.g., benzodiazepines). Because women are exposed to varying levels of progesterone from puberty until menopause, and appear more sensitive to the negative consequences of benzodiazepine use, it is important to understand the impact of progesterone on GABAergic drug effects. Objectives The purpose of this experiment was to characterize the behavioral effects of progesterone, alone and in combination with the short-acting benzodiazepine, triazolam, to determine if progesterone potentiates the behavioral effects of triazolam. Methods Oral micronized progesterone (0, 100, and 200 mg) and oral triazolam (0.00, 0.12, and 0.25 mg/70 kg) were administered to healthy, premenopausal women (n=11) under conditions of low circulating sex hormones. The subjective, performance and physiological effects of progesterone, alone and in combination with triazolam, were assessed. Results Triazolam alone produced prototypical sedative-like effects. Progesterone alone also engendered some sedative effects, although the time course of the effects was more limited than that of triazolam. Progesterone increased and extended the duration of triazolam effects and delayed the onset of triazolam peak effects, most notably at the 0.12 mg/70 kg dose. Conclusions Progesterone potentiates the behavioral effects of benzodiazepines and may contribute to benzodiazepine use and abuse among women.

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“…Peak behavioral effects of 0.25 mg/70 kg triazolam occurred between 1.5 and 2.5 h post-dose, which is consistent with previous reports (e.g., Simpson and Rush 2002; Rush et al 2003). …”

Section: Discussionsupporting

confidence: 91%

Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women

et al. 2011

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“…Consistent with previous studies, triazolam alone engendered a broad range of sedative-like performance impairment and self-reported effects, with peak effects occurring 60 to 90 minutes post dose (Greenblatt et al, 2005; Babalonis et al, 2008; Rush et al, 2003; Simpson & Rush, 2002; Rush & Ali, 1999). Progesterone alone also produced small magnitude increases in sedative-like measures with a similar time course.…”

Section: Discussionsupporting

confidence: 86%

Progesterone effects on the discriminative stimulus, subjective and performance effects of triazolam in healthy, premenopausal women

Babalonis

Lile²,

Martin³

et al. 2011

Behavioural Pharmacology

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There is accumulating evidence that sex plays a critical role in drug abuse. Female sex hormones have been shown to affect central nervous system function and modulate the effects of drugs of abuse. For example, GABAA receptor function is positively modulated by progesterone metabolites. There is evidence from preclinical in vitro and in vivo studies as well as some clinical research suggesting that progesterone and its metabolites may enhance the behavioral effects of benzodiazepines, which also serve as positive modulators of GABAA receptors. The purpose of this experiment was to determine the independent and combined discriminative stimulus, subjective and psychomotor effects of progesterone and triazolam in healthy adult premenopausal women. Oral micronized progesterone (100 mg), triazolam (0.06, 0.12 and 0.25 mg/70 kg) and placebo were administered to healthy, premenopausal women (n =9) under conditions of low circulating sex hormones. Triazolam alone functioned as a discriminative stimulus and produced prototypical sedative-like effects (e.g., performance impairment, enhanced reports of sedative effects). Progesterone alone produced sedative-like effects on several subjective and performance measures and the dose combination effects of progesterone and triazolam on several subjective measures of drug effect were similar to the summation of the two drug effects in isolation. Progesterone did not substitute for or modify the discriminative stimulus effects of triazolam. These results suggest that the parent hormone, progesterone, and triazolam have discordant neuropharmacological mechanisms of action. Additional research is necessary to determine the degree to which neurosteroids influence sex differences in benzodiazepine use and abuse.

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“…However, choice of diazepam differed as a function of drinking status in both studies (i.e., in both of these studies, moderate drinkers self-administered diazepam significantly more than light drinkers). The results of a previous study conducted in our laboratory, by contrast, suggest that moderate and light drinkers are not differentially sensitive to the discriminative-stimulus effects of triazolam, a triazolobenzodiazepine hypnotic (Rush et al, 2003). In this study, six light drinkers and six moderate drinkers were taught to discriminate 0.375 mg of triazolam.…”

mentioning

confidence: 59%

“…Although our findings that light and moderate drinkers respond differentially to the effects of d-amphetamine are provocative, they should be viewed cautiously. As reviewed previously, the results of previous studies that compared the acute behavioral effects of other commonly abused drugs (including ethanol, benzodiazepines, and inhaled anesthetics) in light and moderate drinkers are mixed both within and across laboratories (Cho et al, 1997;de Wit et al, 1989;de Wit and Doty, 1994;Rush et al, 2003;Walker and Zacny, 2001). Future studies should attempt to replicate the results of this experiment and compare the effects of d-amphetamine under other behavioral arrangements (e.g., drug self-administration and discrimination) in light and moderate drinkers.…”

Section: Effects Of Commonly Abused Drugs In Individuals With Differementioning

confidence: 92%

Alcohol Choice and Amphetamine Effects in Light and Moderate Drinkers

Stoops

Fillmore

Poonacha³

et al. 2003

Alcoholism Clin & Exp Res

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Discriminative-Stimulus Effects of Triazolam in Light and Moderate Drinkers

Abstract: Future studies should examine the discriminative-stimulus effects of a lower dose of triazolam (e.g., 0.25 mg) in light and moderate drinks or use a fading procedure to determine differences in terms of the lowest discriminable dose.

Cited by 5 publications

References 27 publications

Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women

Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women

Progesterone effects on the discriminative stimulus, subjective and performance effects of triazolam in healthy, premenopausal women

Alcohol Choice and Amphetamine Effects in Light and Moderate Drinkers

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