Biomedical subjects

H de Wit

Publications and source records attributed to H de Wit.

At least 37 records · Page 2Linked to original sources

PubMed2001

Haloperidol reduces stimulant and reinforcing effects of ethanol in social drinkers.

BACKGROUND: Despite abundant preclinical support for a role of dopamine (DA) in the stimulant-like and reinforcing effects of ethanol, there have been few studies directly investigating this mechanism in human subjects. This study examined the effect of a DA antagonist, haloperidol, on the subjective stimulant-like effects of acute doses of ethanol and on ethanol reinforcement in healthy human volunteers. It was hypothesized that a low dose of the DA D2/D3 antagonist haloperidol (3 mg) would attenuate stimulant-like subjective effects of ethanol (0.75 g/kg) and reduce the number of drinks chosen during a subsequent choice phase. METHODS: Seventeen healthy men and women, 21 to 35 years old, participated in four laboratory sessions conducted at 1-week intervals. During the four sessions they received, in randomized order under double-blind conditions, capsules containing haloperidol or placebo followed by three drinks containing ethanol (0.75 g/kg) or placebo, at 30-min intervals. Subjective and behavioral responses were measured before and after the beverages. After the third beverage, subjects could choose up to five additional doses of the beverage they had ingested. RESULTS: Haloperidol reduced the number of ethanol beverages subjects chose without altering placebo beverage choices. Haloperidol also dampened some of the subjective effects of ethanol, especially in subjects who experienced stimulation after ethanol. Haloperidol reduced stimulant-like and euphorigenic effects of ethanol in subjects who experienced stimulant effects (n = 8) but had no effect in subjects who did not experience stimulation from ethanol (n = 9). CONCLUSIONS: These findings suggest that DA plays a role in the stimulant-like, euphorigenic, and reinforcing qualities of ethanol in humans. However, the findings also raised new questions about the link between the subjective and reinforcing effects of ethanol.

Adult↗

PubMed2000

Naltrexone does not block the subjective effects of oral Delta(9)-tetrahydrocannabinol in humans.

Delta(9)-tetrahydrocannabinol (THC) and opioids have many common effects. In addition, some THC effects in laboratory animals can be blocked or attenuated by opioid antagonists. This suggests that opioid systems mediate or modulate some THC effects. To determine whether opioid systems mediate THC effects in humans, the effects of the opioid antagonist naltrexone on subjective responses to THC were examined in 14 marijuana users. Subjects participated in a double-blinded, cross-over design in which each subject received all combinations of naltrexone (0 or 50 mg) and THC (0, 7.5, or 15 mg). THC increased heart rate and self-reported drug effects, such as euphoria and marijuana-like effects, and decreased psychomotor performance. Naltrexone increased heart rate and decreased self-reported measures of vigor and hunger but did not alter any of the effects of THC. These results suggest that the subjective, physiological, and behavioral effects of THC in humans are not mediated through opioid systems.

Adolescent↗

PubMed2000

Effects of dopaminergic drugs on delayed reward as a measure of impulsive behavior in rats.

RATIONALE: Impulsive individuals exhibit an exaggerated preference for immediate rewards over delayed but larger rewards, perhaps because they value the delayed rewards less. Dopamine (DA) has been postulated to mediate the incentive value of rewards, thus it may also mediate the exaggerated preference for immediate rewards in impulsive individuals. In this paper, we investigate the effects of DA agonists and antagonists on the value of delayed versus immediate rewards. OBJECTIVES: The study had three main objectives: (1) to determine the effects of D1 and D2 type DA antagonists on the value of delayed rewards, (2) to determine the effect of the indirect DA agonist d-amphetamine on the value of delayed rewards, (3) to determine the sensitivity of the adjusting amount (AdjAmt) procedure to acute one-day changes in delay to reward, amount of reward, deprivation level and starting amount. METHODS: In the AdjAmt procedure, rats choose between an adjusting amount of water given immediately (adjusting alternative) and a constant 150 microliters water delayed by 4 s (standard alternative). The immediate amount of water is adjusted across trials until the rat chooses both alternatives with equal frequency (indifference point). The final adjusted amount is an indicator of the subjective value of the standard alternative. RESULTS: The D1/D2 antagonist flupenthixol (25, 50, and 100 micrograms/kg) and the D2 antagonist raclopride (40, 80, and 120 micrograms/kg), decreased the indifference points, whereas the D1 antagonist SCH 23390 (5, 10, and 20 micrograms/kg) did not affect the indifference point. All three DA antagonists slowed responding. The indirect DA agonist amphetamine (0.5, and 1.0 mg/kg) had effects opposite to those of the DA antagonists, it decreased choice latency, increased the number of trials completed and increased the indifference point. Decreasing the water deprivation level (6, 24, and 48 h) had no effect on the indifference points but slowed responding. Increasing the delay to reward (2, 4, and 8 s) and decreasing the amount of water available for choosing the standard alternative (300, 150, 75 microliters) decreased the indifference point. CONCLUSIONS: The results indicate that amphetamine increased the value of delayed rewards (decreased impulsivity) and that D2 but not D1 receptor antagonists decreased the value of delayed rewards (increased impulsivity). The procedure was sensitive to acute 1-day changes in delay and magnitude of reward.

Amphetamine↗

PubMed2000

Effects of ethanol at four phases of the menstrual cycle.

RATIONALE: Ovarian hormones, such as estrogen (E) and progesterone (P), interact with neurotransmitters, such as dopamine and gamma-aminobutyric acid, which are thought to be important in mediating the effects of ethanol. Therefore, it is possible that circulating ovarian hormones influence the acute subjective, behavioral, and physiological effects of ethanol, thus indirectly influencing ethanol consumption. OBJECTIVES: To examine the relationship between hormone levels and consumption of ethanol, this study investigated whether the effects of ethanol and the consumption of ethanol vary as a function of menstrual cycle phase. METHODS: Sixteen healthy women with normal menstrual cycles ingested ethanol at four hormonally distinct phases of the menstrual cycle, namely early follicular, late follicular, mid-luteal, and late-luteal. During each session, they first sampled three small doses of ethanol (0.2 g/kg each) at half-hourly intervals. They completed subjective and behavioral tests before the first dose and after each subsequent dose. After consuming the third beverage, the women were allowed to choose up to three additional doses of ethanol (0.2 g/kg), one every 30 min. RESULTS: Ethanol produced subjective effects typical for this drug (such as stimulant-like effects and euphoria), and it impaired eye movements and psychomotor performance. However, the effects of ethanol did not vary according to menstrual cycle phase, and consumption of ethanol also did not vary across the menstrual cycle. CONCLUSIONS: These results suggest that circulating ovarian hormones, like E and P, have little effect on either the acute subjective and behavioral effects of ethanol, or on ethanol consumption.

Adult↗

PubMed2000

Effects of d-amphetamine and ethanol on a measure of behavioral inhibition in humans.

Little is known about the acute effects of psychoactive drugs on impulsivity and decision making in humans. This study examined the effects of d-amphetamine (AMP; 10 and 20 mg; N = 20) and ethanol (EtOH; 0.2, 0.4, and 0.8 g/kg; N = 17) on the stop task, a putative measure of behavioral inhibition and impulsivity in healthy human volunteers. The stop task provides a measure of the reaction time (RT) needed to inhibit a response (Stop RT [SRT]), relative to the time taken to execute a simple response (Go RT [GRT]). Healthy volunteers performed the stop task before and after receiving one of the drugs. AMP decreased SRT-that is, improved inhibition-only in participants with slow baseline SRTs. EtOH increased SRTs-that is, impaired inhibition-at doses that did not affect GRTs. These results suggest that AMP and EtOH have specific and distinctive effects on the ability to inhibit responses. Impairment in the ability to inhibit responses is thought to reflect a certain form of impulsivity.

Adult↗

PubMed2000

Reward discounting as a measure of impulsive behavior in a psychiatric outpatient population.

Impulsivity has been operationalized as a choice of an immediate smaller reward over a larger delayed or uncertain reward. This study examined a procedure that measures reward preference under these contingencies in psychiatric outpatients considered either at a high or low risk for engaging in impulsive behavior depending on their psychiatric diagnoses. The participants' rates of delay and uncertainty reward discounting were compared with their performances on a behavioral inhibition task and responses on a self-report personality impulsivity measure. The high-risk participants discounted delayed rewards more sharply and scored higher on the self-report impulsivity measure relative to the low-risk participants. Delay and uncertainty discounting were modestly correlated, but no other relationships were found between the other measures. Results from this study indicate that delay-discounting tasks may be sensitive to at least one form of impulsive behavior.

Adult↗

PubMed2000

Laboratory-based assessment of alcohol craving in social drinkers.

Subjective feelings of craving for drugs and alcohol are hallmark symptoms of substance abuse and dependence, and they are thought to play a pivotal role in relapse to drug use. However, relatively little is known about the relationship between craving and overt drug-seeking behavior or drug consumption. One way to investigate the relationship between self-report measures of craving and objective measures of drug-taking behavior is to investigate the degree to which they co-vary in laboratory studies. In particular it may be informative to examine the degree to which these measures co-vary after experimental manipulations that are expected to increase or decrease craving for, or use of, a drug. We review the results of several laboratory studies in which both self-report measures of craving or desire for alcohol and alcohol consumption were measured, using subjects who were non-problem social drinkers. The experimental manipulation used to increase craving and drug-taking was the administration of a priming dose of alcohol. The manipulation that was intended to decrease craving and drug-taking was administration of a dose of naltrexone, because of its use in the treatment for alcoholism. In most of these studies, self-reported ratings of desire for alcohol were positively associated with consumption of alcohol. However, there were also instances in which one measure varied independently of the other, indicating that under certain circumstances they are controlled by separate factors. Laboratory-based studies such as these may improve our understanding of how subjective reports of alcohol craving are related to objective measures of consumption.

Alcohol Drinking↗

PubMed2000

Acute effects of estradiol pretreatment on the response to d-amphetamine in women.

Little is known about the interactions between ovarian hormones and responses to psychoactive drugs in humans. Preclinical studies suggest that ovarian hormones such as estrogen and progesterone have direct and indirect central nervous system actions and that these hormones can influence behavioral responses to psychoactive drugs. In the present study, we assessed the subjective and physiological effects of d-amphetamine (AMPH; 10 mg p.o.) after pretreatment with estradiol. Two groups of healthy, regularly cycling women participated in two sessions scheduled during the early follicular phases of two menstrual cycles. One group received estradiol patches (Estraderm TTS; 0.8 mg) which elevated plasma estradiol levels to approximately 750 pg/ml on both sessions; the other group received placebo patches on both sessions. Both groups received AMPH (10.0 mg) and placebo in a randomized and counterbalanced order on the two sessions. Dependent measures included self-report questionnaires, physiological measures, and plasma hormone levels. Most of the subjective and physiological effects of AMPH were not affected by acute estradiol treatment. Nevertheless, estradiol pretreatment increased the magnitude of the effects of AMPH on subjective ratings of 'pleasant stimulation' and decreased ratings of 'want more'. Also, estradiol produced some subjective effects when administered alone: It increased subjective ratings of 'feel drug', 'energy and intellectual efficiency', and 'pleasant stimulation'. These results provide limited evidence that the stimulating effects of AMPH are increased by acute estradiol pretreatment.

Administration, Cutaneous↗

PubMed2000

Individual differences in the priming effect of ethanol in social drinkers.

OBJECTIVE: Alcohol-dependent individuals frequently report increased desire for alcohol and exhibit increased alcohol-seeking behaviors following a single drink. The phenomenon, known as priming, has been demonstrated in the laboratory in alcohol-dependent humans and in nonhumans, but the effect is inconsistently observed in nonproblem social drinkers. The current experiment examined this effect in healthy, nonproblem social drinkers across a range of preload doses. METHOD: Using a repeated-measures design, 12 social drinkers were given ethanol (0.2, 0.4 or 0.8 g/kg) or placebo preloads. Various subjective effects measures were obtained at regular intervals. In addition, before and after consuming, the preload subjects performed an operant task on which they made repeated choices for either ethanol or money. RESULTS: Ethanol dose-dependently increased subjective reports of drug liking and desire to take more ethanol. When data from all subjects were examined, ethanol did not affect choices for ethanol on the choice task. However, in subjects who reported the greatest positive mood effects from ethanol (0.8 g/kg), the ethanol preload increased choices for ethanol over money on the choice task. CONCLUSIONS: These findings provide evidence for a priming effect of ethanol in social drinkers as measured by increased subjective desire for drug. The findings also suggest that the priming effects may be strongest in individuals who experience the greatest subjective positive mood effects from ethanol.

Adult↗

PubMed2000

Subjective and objective responses to ethanol in moderate/heavy and light social drinkers.

BACKGROUND: Individuals who drink heavily are at an increased risk for adverse consequences of drinking and progression of their drinking habits to abuse or dependence. Therefore, it is important to delineate factors associated with their heavy drinking. METHODS: We examined individual differences in subjective and objective responses to ethanol associated with level of consumption by reanalyzing data from the nine heaviest and nine lightest social drinkers from each of two independently collected subject samples: Holdstock and de Wit (1998) and King et al. (1997). The light drinkers in both samples consumed five or less alcoholic drinks per week, whereas the moderate/heavy drinkers consumed eight or more drinks per week with frequent binge episodes. Acute subjective and objective responses to ethanol (0.6 or 0.8 g/kg) or placebo were compared in the two groups at baseline and during rising and falling blood alcohol concentrations. RESULTS: Moderate/heavy drinkers reported greater stimulant-like and fewer sedative-like and aversive subjective effects after ethanol than did lighter drinkers. These differences occurred in the absence of any group differences in breath alcohol levels, performance effects, or neuroendocrine changes or in overall reports of feeling any drug effects. CONCLUSIONS: These data indicate that habitual moderate/heavy ethanol use was associated with greater stimulant-like effects after an acute dose of alcohol. This finding is consistent with the idea (Newlin and Thomson, 1990, 1999) that individuals who experience greater stimulant-like effects during the ascending limb and lesser sedative-like effects on the descending limb of the blood alcohol concentration curve may be at greater risk for developing ethanol use disorders. Although we cannot determine the causality of this association, sensitivity to the stimulant effects of ethanol may play an important role in the continuation of heavy ethanol use and the increased risk of negative consequences from this use.

Adrenocorticotropic Hormone↗

PubMed1999

Non-specific effect of naltrexone on ethanol consumption in social drinkers.

RATIONALE: Clinical studies have shown that the opioid antagonist naltrexone is effective in the treatment of alcoholism. However, the mechanism by which it produces this effect is not understood. OBJECTIVE: This study was designed to investigate the effect of acute naltrexone on consumption of ethanol in healthy, non-problem social drinkers. METHODS: Subjects (n=24) participated in an eight-session, within-subject, placebo-controlled choice procedure which measured ethanol preference and consumption. The procedure consisted of two blocks of four sessions in which subjects received either naltrexone (50 mg oral) or placebo 1 h before consuming an ethanol or placebo beverage. On the first two sessions of each block, subjects received a color-coded beverage containing ethanol (0.75 g/kg) or placebo, in five equal portions at 15-min intervals. On the next two sessions of each block, subjects chose which beverage they preferred (i.e., placebo or ethanol) and how much they wished to take, in unit doses (placebo or ethanol 0.15 g/kg/dose). The primary behavioral measures were (1) the number of times subjects chose ethanol over placebo, and (2) the number of doses they consumed. Subjects rated their mood states and subjective drug effects at regular intervals during each session. RESULTS: Naltrexone did not alter the frequency of ethanol (versus placebo) choice. Although naltrexone did decrease the total number of ethanol doses subjects took (mean 2.7 doses after naltrexone; 3.4 doses after placebo), it also decreased the number of placebo "doses" subjects took on sessions when they chose the placebo beverage (mean 1.6 placebo doses after naltrexone; 2.8 doses after placebo). Ethanol produced its prototypic subjective effects (e.g., increased ratings of "feel drug", "like drug" and "high"), and these effects were not altered by naltrexone. Naltrexone produced mild sedative-like effects, and several subjects reported adverse effects such as nausea. CONCLUSIONS: These findings show that naltrexone reduces ethanol consumption in healthy volunteers, as it does in alcoholics. However, this reduction was not specific to alcohol; subjects also consumed less of a non-alcoholic, placebo beverage. These findings suggest that naltrexone may reduce alcohol consumption by a non-specific mechanism.

Adult↗

PubMed1999

Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats.

RATIONALE: Moderate doses of d-amphetamine (given both acutely and chronically) have been shown to decrease impulsivity in children with attention deficit hyperactivity disorder (ADHD) and to improve attention and learning in normal adults. In contrast, chronic doses of methamphetamine (METH) in drug abusers have been associated with increased impulsivity, and impairments in learning and attention. OBJECTIVES: We report the effects of METH on an animal model of impulsive behavior. METHODS: Rats were tested using the adjusting amount (AdjAmt) procedure in which the animals choose between a delayed fixed (large) amount of water and an immediate adjusting (small) amount of water. In the acute METH study, rats were given a single dose of 0.5, 1.0, 2.0, and 4.0 mg/kg METH or saline 30 min before testing. In the chronic METH study, we determined the effects of the 4.0 mg/kg dose of METH injected chronically 1 h after behavioral testing for 14 days. Thus the rats were tested using the AdjAmt procedure 22 h after injections of METH or saline. RESULTS: After 0.5, 1.0 and 2.0 mg/kg METH, the rats valued the delayed large rewards more than after saline, indicating that the METH decreased impulsiveness. At the 4.0 mg/kg dose, the rats failed to respond. Rats treated repeatedly with the post-session large behaviorally disruptive dose of METH valued the delayed large rewards less than the saline-treated rats, indicating that this dosing regimen of METH increased impulsiveness. CONCLUSIONS: In these experiments, the rats became less impulsive after acute non-disruptive doses of pre-session METH, whereas they became more impulsive after receiving repeated post-session injections of a dose that was behaviorally disruptive when administered acutely.

Animals↗

PubMed1999

Acute effects of d-amphetamine during the follicular and luteal phases of the menstrual cycle in women.

RATIONALE: Little is known about the interactions between ovarian hormones across the menstrual cycle and responses to psychoactive drugs in humans. Preclinical studies suggest that ovarian hormones such as estrogen and progesterone have direct and indirect central nervous system actions, and that these hormones can influence behavioral responses to psychoactive drugs. OBJECTIVES: In the present study, we assessed the subjective and behavioral effects of d-amphetamine (AMPH; 15 mg orally) at two hormonally distinct phases of the menstrual cycle in women. METHODS: Sixteen healthy women received AMPH or placebo capsules during the follicular and mid-luteal phases of their cycle. During the follicular phase, estrogen levels are low initially and then rise while progesterone levels remain low. During the midluteal phase, levels of both estrogen and progesterone are relatively high. Dependent measures included self-report questionnaires, physiological measures and plasma hormone levels. RESULTS: Although there were no baseline differences in mood during the follicular or luteal phase, the effects of AMPH were greater during the follicular phase than the luteal phase. During the follicular phase, subjects reported feeling more "High", "Energetic and Intellectually Efficient", and "Euphoric" after AMPH than during the luteal phase, and also reported liking and wanting AMPH more. Further analyses showed that during the follicular phase, but not the luteal phase, responses to AMPH were related to levels of estrogen. Higher levels of estrogen were associated with greater AMPH-induced increases in "Euphoria" and "Energy and Intellectual Efficiency". During the luteal phase, in the presence of both estrogen and progesterone, estrogen levels were not related to the effects of AMPH. CONCLUSIONS: These findings suggest that estrogen may enhance the subjective responses to a stimulant drug in women, but that this effect may be masked in the presence of progesterone.

Adolescent↗

PubMed1999

Responses to oral delta9-tetrahydrocannabinol in frequent and infrequent marijuana users.

It is known that an individual's drug use history affects the quality of subjective effects experienced following administration of several clinically used psychoactive drugs such as barbiturates, diazepam, and morphine. However, it is not known whether drug use history also affects responses to therapeutic cannabinoids such as delta9-THC. The current experiment compared the subjective and behavioral effects of oral delta9-THC in two groups of volunteers: frequent users (FREQ; n = 11), who reported using marijuana at least 100 times, and infrequent users (INF; n = 10) who reported using marijuana 10 or fewer times. Subjects participated in three sessions during which they received delta9-THC (7.5 and 15 mg) and placebo. They completed subjective effects questionnaires for 5 h following administration. In the FREQ group, the lower dose (7.5 mg) increased ratings of "feel drug," relative to placebo, whereas it had no effect in the INF group. In contrast, at the higher dose (15 mg), ratings of "feel drug" were lower in the FREQ group than in the INF group, suggestive of tolerance. In addition, the INF group reported greater sedative effects than the FREQ group following the higher dose of delta9-THC, again suggesting tolerance to delta9-THC's sedative effects. These findings demonstrate that marijuana use history may affect the subjective effects of oral delta9-THC, but that the influence of drug use history depends on the dose of drug administered. These findings may have implications for the clinical use of delta9-THC and other cannabinoids.

Administration, Oral↗

PubMed1999

Synaptic vesicles form by budding from tubular extensions of sorting endosomes in PC12 cells.

The putative role of sorting early endosomes (EEs) in synaptic-like microvesicle (SLMV) formation in the neuroendocrine PC12 cell line was investigated by quantitative immunoelectron microscopy. By BSA-gold internalization kinetics, four distinct endosomal subcompartments were distinguished: primary endocytic vesicles, EEs, late endosomes, and lysosomes. As in other cells, EEs consisted of vacuolar and tubulovesicular subdomains. The SLMV marker proteins synaptophysin and vesicle-associated membrane protein 2 (VAMP-2) localized to both the EE vacuoles and associated tubulovesicles. Quantitative analysis showed that the transferrin receptor and SLMV proteins colocalized to a significantly higher degree in primary endocytic vesicles then in EE-associated tubulovesicles. By incubating PC12 cells expressing T antigen-tagged VAMP (VAMP-TAg) with antibodies against the luminal TAg, the recycling pathway of SLMV proteins was directly visualized. At 15 degrees C, internalized VAMP-TAg accumulated in the vacuolar domain of EEs. Upon rewarming to 37 degrees C, the labeling shifted to the tubular part of EEs and to newly formed SLMVs. Our data delineate a pathway in which SLMV proteins together with transferrin receptor are delivered to EEs, where they are sorted into SLMVs and recycling vesicles, respectively.

Animals↗

PubMed1999

Effects of triazolam at three phases of the menstrual cycle.

This study investigated the subjective and behavioral effects of a commonly used benzodiazepine, triazolam, in healthy women at three phases of the menstrual cycle: follicular, periovulatory, and luteal. Ovarian hormones or their metabolites have direct and indirect actions on neuronal receptors, which may affect responses to psychoactive drugs acting on the same central nervous system receptors. This study explored the effect of menstrual cycle phase on the mood-altering and performance effects of a single oral dose of the benzodiazepine triazolam. Twenty women received triazolam (0.25 mg orally) or placebo at the follicular, periovulatory, and luteal phases of their menstrual cycles in a within-subject design. Dependent measures included self-reported mood states, psychomotor performance, and plasma levels of triazolam, estradiol, progesterone, and allopregnanolone. After administration of triazolam, most subjects reported the expected increases in fatigue and decreases in arousal and psychomotor performance. Neither plasma levels nor mood and performance effects of triazolam differed across the three phases. This study illustrates a useful methodology for assessing responses to psychoactive drugs in normally cycling women and shows that the effects of this drug were highly stable across the cycle.

Adolescent↗

PubMed1999

Subjective and behavioral effects of repeated d-amphetamine in humans.

Behavioral sensitization is thought to be an important determinant of drug-taking and drug-seeking behaviors. Although there is abundant research characterizing behavioral sensitization in animals, there is little evidence for this phenomenon in humans. The aim of the present study was to determine if repeated oral d-amphetamine administration enhances self-reported mood and other behavioral indices of d-amphetamine effects in humans. Sixteen healthy volunteers, with no prior stimulant use, received two doses of d-amphetamine (20 mg) and two doses of placebo, in alternating order, on 4 consecutive days, under double-blind conditions. Mood and behavioral effects were measured using standard self-report questionnaires. Heart rate, blood pressure, psychomotor performance, and tapping speed were also monitored. d-Amphetamine elicited prototypical increases on several measures including self-reported drug effects, mood, and physiological responses. However, except for a slight reduction in 'feel drug' scores during the first hour of the second d-amphetamine session, the majority of effects were not altered on the second session. These results indicate that the subjective effects of d-amphetamine display only an apparent mild tolerance after a single exposure 48 h earlier.

Adult↗

PubMed1999

Individual differences in subjective responses to ethanol and triazolam.

This study evaluated the relationship between sedative-like subjective responses to ethanol and triazolam in normal, healthy volunteers. It was hypothesized that subjects' responses to the two drugs would be correlated, because of the common mechanism of action of the drugs at the GABAA receptor complex. Twenty-seven volunteers (14 male, 13 female), aged 21-35 years, received beverages or capsules containing ethanol (0.2, 0.4 or 0.8 g/kg), triazolam (0.125, 0.25 or 0.5 mg) or placebo (two sessions) on eight separate sessions in a random order. Various self-reported and objective drug effects were measured, including measures of sedative-like subjective effects, as indexed by the ARCI PCAG scale. PCAG scores of individual subjects across the three active doses of each drug were fitted with a straight line function (y = a + bx), and the correlation of the slopes from the fitted curves for ethanol and triazolam was examined. Among the participants who reported any sedative-like responses to ethanol, the sedative-like effects of ethanol and triazolam were positively correlated. That is, subjects who exhibited the steepest dose-related effects on measures of subjective sedation after ethanol also exhibited the steepest slopes after triazolam. These findings provide partial support for the idea that ethanol and triazolam produce their sedative-like effects through the same mechanism.

Adult↗