Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

Aim

The pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg^–1 alcohol using 40% vodka).

Methods

In a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration.

Results

Alcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated.

Conclusion

SMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed.     

Alcohol-induced changes in body sway in women at risk for alcoholism: a pilot study

Family history of alcoholism appears to influence acute alcohol responses in young men. We report pilot data from a study designed to expand these observations by measuring blood alcohol levels (BALs), subjective intoxication effects, body sway and cognitive-motor task performance in women. Six young women with (FHP) and six without (FHN) alcoholic first degree relatives provided informed consent and were given 0.56 g/kg ethanol under double-blind conditions. Groups were matched for age, drinking history and height-weight ratio. Subjects performed tasks in random order at 90, 60 and 30 min before drinking alcohol, and 15, 30, 45, 60, 90, 120, 150 and 180 min after drinking alcohol. BALs peaked at 80 mg/dl 30 to 60 min after drinking alcohol. BALs were comparable and disappearance rates were similar for both groups. BALs and intoxication ratings for both FHP and FHN women had highly significant correlations. Alcohol decreased accuracy on an automated version of the Digit Symbol Substitution Test (DSST) for both groups, but FHN women made significantly more errors 30 min after alcohol. Significantly greater alcohol effects on body sway were apparent in FHN women 15, 30, 60, 90 and 120 min after alcohol. Compared with previous findings for men, both FHP and FHN women reported less intoxication at similar BALs, but body sway in FHN women was more affected by alcohol. Small sample size limits generalization of these findings but suggests that some effects of familial alcoholism in women are similar to those observed in men.     

Pharmacokinetic and pharmacodynamic interactions of diazepam with different alcoholic beverages

Summary Twenty paid healthy students ingested diazepam 10 mg 30 min after the administration of ethanol 0.8 g/kg. The alcoholic beverage used was varied in randomized double-blind experiments, which were repeated at one-month intervals. Psychomotor performance, plasma diazepam, and alcohol concentration in breath were measured 30, 60, 90 min and 2, 3, 4, 6 and 24 h after the ingestion of diazepam. Beer and white wine elevated the plasma level of diazepam and the effect lasted for up to 2 h. Whisky elevated the diazepam level for 90 min. Red wine did not affect it significantly. The alcohol-diazepam combination impaired tracking skills and oculomotor co-ordination and enhanced nystagmus, more than diazepam alone. Red wine produced a breath alcohol concentration higher than after white wine. More nystagmus was recorded after red wine and diazepam, although white wine led to a higher plasma diazepam concentration. It appears that simultaneous ingestion of alcohol and diazepam accelerates the absorption of diazepam. This pharmacokinetic alteration may not contribute much to the combined psychomotor effects of diazepam and alcohol, which were mainly due to pharmacodynamic interaction at receptor level.     

Time relations of the effects of alcohol compared to placebo

Summary 31 healthy male students were given a placebo and two different doses of alcohol (on different occasions and in random order). Choice-reaction-time, tapping-speed, bimanual hand-coordination, critical fusion frequency, standing steadiness, Bourdon's test, blood and urine alcohol content were measured before and 30, 60 and 90 min after drinking. Self-ratings of mood were made. 7 of the subjects were also examined after 2, 3 and 13 hours and altogether 4 doses of alcohol were used for this group. 24 subjects were given an additional dose of alcohol 2 hours after the first one and the tests were repeated 30, 60 and 90 min after the additional dose. The agreement between blood and urine alcohol levels was good and the alcohol curves showed an approximately linear fall-off. For the highest alcohol dose used there was a good agreement between blood alcohol level and test performance. The impairment of performance was most marked after 30–60 min. After 2 hours the impairment was very slight. The performance on Choice reaction time and Coordination was related to blood alcohol level also after a smaller dose. Statistically significant changes were obtained in most tests after the highest dose (0.8 g per kg body weight) and in Choice reaction time and Coordination after the smaller dose (0.4 g per kg body weight). No significant effects were obtained after administration of placebo.     

Subjective and cardiovascular responses to nicotine combined with alcohol in male and female smokers

Nicotine and alcohol are often consumed concurrently by smokers. Each drug alone produces significant subjective and cardiovascular responses, but the effects of the two drugs in combination have rarely been examined. Smokers who were moderate alcohol drinkers (n = 18, 9 males and 9 females) participated in four sessions, involving acute administration of nicotine/placebo and alcohol/no alcohol. Subjects abstained overnight from tobacco and alcohol prior to each session. Nicotine (20 µg/kg per presentation) or placebo was administered by measured-dose nasal spray every 30 min for 2 h following consumption of diet tonic water with or without alcohol (0.5 g/kg). Subjective (visual analog scales, Profile of Mood States, Addiction Research Center Inventory) and cardiovascular (heart rate, systolic and diastolic blood pressure) responses were assessed after each nicotine/placebo administration. Nicotine increased head rush, dizzy, and most stimulant effects (i.e. jittery, tension, and arousal and decreased fatigue and relaxed), while alcohol increased intoxication, head rush, dizzy, and jittery, with no other stimulant effects. Nicotine and alcohol generally produced additive subjective and cardiovascular effects when consumed together, although nicotine attenuated sedating and intoxicating effects of alcohol alone. Furthermore, there were several interaction effects on subjective measures involving gender. Nicotine plus alcohol tended to attenuate some subjective effects due to one drug or the other alone in men but enhanced the effects of either alone in women. These findings indicate that nicotine and alcohol generally have additive subjective and cardiovascular effects, but that men and women differentially respond on some subjective measures to the combination of alcohol and nicotine.     

Time course of the locomotor stimulant and depressant effects of a single low dose of ethanol in mice

The acute effects of alcohol on spontaneous locomotor activity in male Swiss mice were studied at various times after an IP injection of 2 g/kg ethanol. Subjects were placed alone in a novel arena and videotape recordings were made of behaviour: trials were of 500-s duration and commenced at either 30, 60, 120, or 180 min after alcohol administration. Measures of behaviour included various indices of ambulation and immobility, together with a more detailed ethological analysis of the frequencies of all other acts and postures shown by test animals. Ambulation showed a biphasic response to alcohol treatment, consisting of an initial stimulation followed by a suppression after 3 h. Immobility was also increased by alcohol, and showed peak stimulation in trials commencing 30 min after administration: thereafter there was a progressive return to baseline levels. Many behavioural elements were suppressed including rearing, digging, shaking, and abbreviated grooming. Ethanol thus appeared to produce two distinct types of depression, in terms of increased immobility (and suppression of other behaviour) and in terms of decreased ambulation, the latter occurring when immobility had returned to baseline levels.     

Time-course of changes in the social interaction test of anxiety following acute and chronic administration of nicotine

The purpose of these experiments was to explore the hypothesis that the effects of nicotine on anxiety depend on the time since administration and the duration of treatment. In the social interaction test of anxiety, acute nicotine administration (0.1 mg/kg, subcutaneously) decreased social interaction when rats were tested 5 min after injection, but increased it when they were tested 30 min after injection. Social interaction was also decreased 1 h post-injection, but levels returned to baseline between 3 and 30 h. As these changes were independent of any changes in locomotor activity, nicotine seemed to be having both anxiogenic and anxiolytic effects at different times after injection. An anxiolytic effect was also observed 30 min after the second nicotine injection, and the anxiogenic effect observed 5 min after injection remained after 4 days of nicotine administration. However, after 7 days of nicotine treatment, tolerance was observed to both these effects. When rats were tested 72 h after the last of 7 or 14 days of nicotine treatment, an anxiogenic withdrawal response was observed. Thus, an oppositional mechanism may underlie tolerance to the anxiolytic effects, whereas there is as yet no evidence for this type of mechanism mediating tolerance to the anxiogenic effects.     

The role of impulsivity and perceived availability on cue-elicited craving for alcohol in social drinkers

Rationale

Previous research has demonstrated a role for impulsivity and perceived availability of the substance in cue-elicited craving. However, their effects on cue-elicited craving for alcohol are still ambiguous. Most important is that there has been no empirical evidence for the potential interaction of these factors on alcohol craving.

Objectives

The aim of the present study was to examine the effects of response inhibition and perceived availability on cue-elicited craving for alcohol in social drinkers.

Methods

Participants were light to moderate social drinkers (N?=?75) who were exposed to neutral- and alcohol-related stimuli during a single laboratory session. Response inhibition was assessed with the Stop Signal Task. Participants were randomly assigned to one of two perceived availability groups (n?=?37, expecting alcohol; n?=?38, not expecting alcohol).

Results

Overall craving for alcohol was higher in participants who expected alcohol than in those who did not. This finding was statistically significant only in the alcohol condition. Most important is that there was a significant interaction between response inhibition, perceived availability and time on cue-elicited craving. Regardless of the cue type, impulsive people who expected alcohol experience a significant increase in cue-elicited craving relative to impulsive people who did not expect alcohol. This effect was not observed in the non-impulsive groups.

Conclusions

The results clearly show that perceived availability alone and in combination with response inhibition can modulate alcohol cue reactivity. Theoretical explanations and clinical implications of these findings are discussed.     

Effects of sibutramine alone and with alcohol on cognitive function in healthy volunteers

AIMS: To investigate the effects of sibutramine in combination with alcohol in a double-blind, randomised, placebo-controlled, four-way crossover study in 20 healthy volunteers. METHODS: On each study day each volunteer received either: sibutramine 20 mg+0.5 g kg-1 alcohol; sibutramine 20 mg+placebo alcohol; placebo capsules+0.5 g kg-1 alcohol; or placebo capsules+placebo alcohol. Alcohol was administered 2 h following ingestion of the study capsules. During each study day, assessments of cognitive performance were made prior to dosing, and at 3, 4.5, 6 and 10 h post dosing. Blood alcohol concentration was estimated using a breath alcometer immediately prior to each cognitive performance test session. Each study day was followed by a minimum 7 day washout period. RESULTS: Alcohol was found to produce statistically significant impairments in tests of attention (maximum impairment to speed of digit vigilance=49 ms) and episodic memory (maximum impairment to speed of word recognition=74 ms). Alcohol also increased body sway (maximum increase 17.4 units) and lowered self rated alertness (maximum decrease 13.6 mm). These effects were produced by an inferred blood alcohol level of 53.2 mg dl-1. Sibutramine was not found to potentiate any of the effects of alcohol. There was a small, yet statistically significant, interaction effect observed on the sensitivity index of the picture recognition task. In this test, the combined effects of sibutramine and alcohol were smaller than the impairments produced by alcohol alone. Sibutramine, when dosed alone, was associated with improved performance on several tasks. Sibutramine improved attention (mean speed of digit vigilance improved by 21 ms), picture recognition speed (improvement at 3=81) and motor control (tracking error at 3 h reduced by 1.58 mm). Also sibutramine improved postural stability (reducing body sway at 3 h by 14.2 units). Adverse events reported were unremarkable and consistent with the known pharmacology of sibutramine and alcohol. CONCLUSIONS: There was little evidence of a clinically relevant interaction of sibutramine with the impairment of cognitive function produced by alcohol in healthy volunteers. The single statistically significant interaction indicated a reduction, rather than a worsening, of alcohol-induced impairment when sibutramine is taken concomitantly. Sibutramine when administered alone is associated with improved performance on several tasks.     

Drug effects on psychomotor skills related to driving: Interaction of atropine,glycopyrrhonium and alcohol

Summary Atropine 0.5 mg and glycopyrrhonium 1.0 mg in combination with alcohol or a placebo drink were administered double blind to 170 healthy young volunteers, and certain psychomotor skills were measured by a choice reaction test, two coordination tests, and an attention test. The drugs were administered 30 min before the test and the tests were repeated 90 and 150 min after dosing. Both atropine and glycopyrrhonium shortened reaction time and either left co-ordination unaffected or slightly improved. Anticholinergics or alcohol alone impaired attention. The combination of anticholinergics and alcohol further impaired attention whilst leaving reaction times and co-ordination unaffected. The interaction of atropine and alcohol differed only slightly from that of glycopyrrhonium and alcohol.     

Effects of the 5-HT2B receptor agonist, BW 723C86, on three rat models of anxiety.

1. BW 723C86 (3 and 10 mg kg-1, s.c. 30 min pretest), a 5-HT2B receptor agonist, increased total interaction, but not locomotion in a rat social interaction test, a profile consistent with anxiolysis. 2. The effect of BW 723C86 in the social interaction test is likely to be 5-HT2B receptor-mediated as it was prevented by pretreatment with the 5-HT2C/2B receptor antagonist, SB 200646A, (1 and 2 mg kg-1, p.o., 1 h pretest) which did not affect basal levels of social interaction at the doses used. 3. An anxiolytic-like action was also observed in the rat Geller-Seifter conflict test, where BW 723C86 (0.5-50 mg kg-1, s.c. 30 min pretest) modestly, but significantly increased punished, but not unpublished responding. 4. In a rat 5 min elevated x-maze test, BW 723C86 (1-10 mg kg-1, s.c.) had no significant effect. 5. The maximal anxiolytic-like effect of BW 723C86 approached that of the benzodiazepine anxiolytic, chloradiazepoxide (5 mg kg-1, s.c. 30 min pretest) in the social interaction test, but was markedly less in the Geller-Siefter test. The effect of BW 723C86 was also clearly less than chlordiazepoxide in the elevated x-maze procedure where it had no significant effect. 6. In conclusion, BW 723C86 exerted an appreciable anxiolytic-like profile in a rat social interaction test, but had a weaker effect in the Geller-Siefter and was ineffective in the elevated x-maze test used. These effects are likely to be 5-HT2B receptor-mediated.     

Detecting impairment associated with cannabis with and without alcohol on the Standardized Field Sobriety Tests

Rationale

Cannabis and alcohol are the most popular drugs amongst recreational users and most prevalent in injured and deceased drivers. The Standardized Field Sobriety Tests (SFST) are commonly used to establish impairment due to drugs and alcohol, but limited empirical evidence exists concerning the combined effects of these drugs on SFST performance.

Methods

The sample comprised 80 individuals (31 females; 49 males). Age ranged between 21 and 35?years (M?=?26.5, SD?=?5). Forty participants (15 females; 25 males) took part in the low alcohol condition (BAC, <0.05?%), and 40 participants (16 females; 24 males), took part in the high alcohol condition (BAC, >0.05?%). For each part of the study, two levels of ?9-tetrahydrocannabinol (THC) were administered (1.8 and 3?% THC) or a matching placebo cigarette (0?% THC) in combination with alcohol. Performance on the SFST was assessed 30?min post-dosing.

Results

A number of significant differences in SFST performance were identified with 28?% of the sample failing the test (when the head movement and jerks sign was included) when low alcohol and low THC were administered together. When a higher dose of alcohol was administered with a low dose of THC, 38?% of the sample failed the test, and 35?% also failed when the high dose of alcohol was combined with a higher dose of THC.

Conclusions

The current results highlight the limited ability of the SFST to identify drug consumption in the absence of any evidence of driving impairment or physiological indicators.     

Naltrexone effects on diazepam intoxication and pharmacokinetics in humans

 The opiate antagonist naltrexone (NTX) blocks relapse drinking in alcoholics and modifies some of the subjective effects of alcohol intoxication. Benzodiazepines have demonstrated cross-dependence and cross-tolerance to alcohol. Furthermore, benzodiazepine intoxication has effects on mood and psychomotor performance that are similar to alcohol intoxication. The effects of NTX on diazepam intoxication were investigated in non-drug abusing individuals. Eighteen men and eight women were randomly assigned to receive either 50 mg NTX or placebo PO, on two different occasions in a within-subjects, cross-over, double-blind protocol. Diazepam was taken by mouth, 90 min after NTX. At −90, 45, 75, 135, 210 min, subjects were tested with repeated assessments of several mood and sensation scales and a computer-generated psychomotor test battery (CTB). Blood samples were also obtained and analyzed for serum diazepam levels. Diazepam induced several sensations and mood effects similar to those induced by alcohol. Negative mood states such as sedation, fatigue, and anxiety were higher for NTX than for placebo. Positive mood states such as friendliness, vigor, liking the effects of diazepam, and feeling high from diazepam were all lower for NTX than for placebo. There were no group differences on the CTB performance. NTX delayed the time to reach peak diazepam levels, so that peak levels occurred at 75 min for placebo compared to 135 min for NTX. A sub-analysis was conducted with 14 subjects who were FHP for alcoholism, but no differences were found on these outcome measures. Received: 31 March 1997/Final version: 10 July 1997     

Contingent tolerance to the disruptive effects of alcohol on the copulatory behavior of male rats.

Sexually active male rats received five 30-min copulation tests with sexually receptive females, one every 4 days. One group of rats received alcohol (1 g/kg, IP) 45 min before, and an equivalent volume of saline 45 min after, each test; a second group received saline before and alcohol after each test; and a third, control group received saline both before and after. Four days after the last of the five tolerance-development trials, each rat received an injection of alcohol (1 g/kg, IP) 45 min before a copulation test so that the development of tolerance in the three groups could be compared. Tolerance to the disruptive effects of alcohol on mount, intromission, and ejaculation latencies, and on the duration of the postejaculatory interval was found to be significantly greater in the rats injected with alcohol before each copulation test than it was in the rats in the other two groups. These results constitute the first experimental evidence that tolerance develops to the disruptive effects of alcohol on male sexual behavior, and they support the theory that tolerance is an adaptive response to the disruptive effects of drugs on concurrent patterns of neural activity, rather than to drug exposure per se.     

Influence of the menstrual cycle on flight simulator performance after alcohol ingestion

OBJECTIVE: Previous studies investigating the influence of the menstrual cycle on cognitive functioning of women after alcohol ingestion have obtained inconsistent results. The present study tested the hypothesis that flight simulator performance during acute alcohol intoxication and 8 hours after drinking differs between the menstrual and the luteal phase of the menstrual cycle. METHOD: White female pilots (N = 24) were tested during the menstrual and the luteal phases of their menstrual cycles. On each test day they performed a baseline simulator flight, consumed 0.67 g/kg ethanol, and performed an acute-intoxication and an 8-hour-carryover simulator flight. RESULTS: Subjects reached highly significant increases in estradiol (E2) as well as progesterone (P) levels during the luteal test day. Yet, there were no significant differences in overall flight performance after alcohol ingestion between the menstrual and luteal phases during acute intoxication or at 8-hour carryover. We found no correlations between E, or P levels and overall flight performance. However, there was a statistically significant Phase x Order interaction: Pilots who started the experiment with their menstrual day were less susceptible to the effects of alcohol during the second test day than were pilots who started with their luteal day. CONCLUSIONS: The tested menstrual cycle phases and varying E2 and P levels did not significantly influence postdrink flight performance. Because the present study included a comparatively large sample size and because it involved complex "real world" tasks (piloting an aircraft), we believe that the present findings are important. We hope that our failure to detect menstrual cycle effects will encourage researchers to include women in their investigations of alcohol effects and human performance.     

Comparison of deramciclane to benzodiazepine agonists in behavioural activity of mice and in alcohol drinking of alcohol-preferring rats

Interactions between alcohol and traditional benzodiazepine anxiolytics hamper the treatment of alcoholism-related anxiety disorders. Serotonin 5-HT(2) receptor antagonists, such as deramciclane, are anxiolytic, and considering their pharmacological profile, they might benefit alcoholics with comorbid anxiety. We studied the effects of acute deramciclane (1, 3 and 10 mg/kg i.p.) on alcohol drinking of alcohol-preferring AA rats drinking 10% (vol/vol) ethanol solution in a 4-h limited-access paradigm. Thereafter, a 5-day repeated-treatment experiment was carried out, under corresponding test design, with deramciclane (3 mg/kg i.p.) as a test drug and midazolam (1 mg/kg i.p.) as a benzodiazepine reference compound. Deramciclane had no effect on alcohol consumption in either acute or repeated dosing study. Midazolam increased ethanol drinking, as expected, when administered on successive days. A modified functional observational battery (FOB) procedure was applied to study neurological, behavioural and autonomic effects induced by deramciclane (1-30 mg/kg po) and diazepam (1-30 mg/kg po) in mice at 30 min, 2 h and 4 h after dosing. Deramciclane had a mild dopamine D(2) receptor antagonism-like effect at the highest dose. The effects of diazepam were predictable, myorelaxation-induced motor impairment and anxiolysis-related hyperlocomotion in a novel environment being the characteristic features at the two highest doses. Deramciclane appears to be a safe and well-tolerated drug and we suggest that it might be useful in the treatment of anxiety in alcoholics.     

Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects

The interaction of clomipramine and moclobemide with alcohol was compared in a double blind parallel groups study in 24 healthy volunteers. Moclobemide was given at the highest recommended therapeutic dose (200 mg t.i.d.) and clomipramine in a subtherapeutic dose (25 mg b.i.d.) because of its poor tolerance in healthy subjects. Psychometric evaluations were performed during a placebo run-in phase; after a 5-day treatment period; assessments were made before, and again 1 h and 4 h after alcohol ingestion. Alcohol doses were pre-determined for each subject in order to produce a blood alcohol concentration of 0.6 g/l 1 h after alcohol intake and this individual alcohol dose was given on test days. The day before alcohol intake tests for autonomic functions were made to assess the anticholinergic effects of the drugs. Alcohol significantly increased body sway, decreased critical flicker fusion frequency, prolonged choice reaction time, impaired copying skills, impaired memory and increased the subjective feelings of satisfaction and tension. Drugs increased the effect of alcohol on body sway and this was essentially due to clomipramine. Clomipramine both without and with alcohol increased body sway, prolonged choice reaction time more than did moclobemide. Clomipramine seemed to diminish alcohol-induced memory impairment in one of the memory tests used. Subjects taking clomipramine had significantly more adverse effects after alcohol ingestion than did subjects of the moclobemide group. In contrast to moclobemide, clomipramine produced a moderate but significant drop in standing systolic blood pressure and a clear inhibition of salivary excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute tolerance to the ataxic effects of ethanol in short-sleep (SS) and long-sleep (LS) mice

 The objective of this series of studies was to examine the relationship between alcohol sensitivity and the development of very rapid acute tolerance to alcohol in mice. In order to measure acute tolerance to alcohol, a behavioral test was developed using a rotorod. In the first study, mice selectively bred for resistance (short sleep, SS) or sensitivity (long sleep, LS) to the acute hypnotic effects of ethanol were used, as well as mice from the base population (heterogenous stock, HS). Mice were trained to run on the rotorod at a speed of 14 rpm to a criterion of 200 s, in four daily training sessions. On the test day, baseline measurements of rotorod performance were taken and mice were injected IP with alcohol in doses from 0 to 2.5 g/kg. Animals were tested at 1-min intervals for the first 5 min following injection, then at 5-min intervals for a total of 30 min. The results demonstrated that SS and HS mice developed tolerance within 10 min following the alcohol injections. LS mice did develop some acute tolerance, but at a much slower rate than the SS or HS mice. In the second study, the effects of intoxicated practice on the rates of acute tolerance development were examined in the SS, HS and LS mice at a dose of 2.0 g/kg alcohol. A total of ten groups of each strain were given a different number of practice trials (ranging from one to ten) on the rotorod prior to a final test session at 30 min post-injection. The results provide evidence that SS and HS mice are capable of developing acute tolerance independent of practice. That is, the group of animals injected at 0 time and tested ten times up to 30 min were no better at the 30-min time point than the group injected at 0 time and tested only once at 30 min. On the other hand, the LS mice showed a modest practice effect, developing additional tolerance to the ataxic effects of alcohol with increasing intoxicated practice. Overall, these studies demonstrated that mice can develop acute tolerance within minutes following alcohol exposure, and that this ability is correlated with the initial sensitivity to alcohol. Received: 12 July 1997 / Final version: 26 August 1997     

Sex differences in stimulus expectancy and pharmacologic effects of a moderate dose of alcohol on smoking lapse risk in a laboratory analogue study

Rationale

Alcohol use is often implicated in initial lapses to smoking during quit smoking attempts. Mechanisms explaining this association are unknown but could include (a) learned associations between drinking and smoking or (b) direct pharmacologic effects of alcohol.

Objectives

In a 2 (told alcohol vs. told placebo)?×?2 (0.4?g/kg vs. 0.0?g/kg ethanol) between-subjects balanced placebo design, we examined instruction and beverage condition effects on smokers?? ability to resist initiating smoking and whether these effects differed by sex.

Methods

Participants were 96 heavy alcohol drinkers, smoking 10?C30 cigarettes per day. After 15?h of smoking abstinence, participants consumed either an alcoholic or a nonalcoholic beverage and 35?min later completed a smoking lapse task.

Results

Overall, neither instructions nor beverage contents influenced behavior on the smoking lapse task. However, the instruction condition had different effects in men and women. Women, but not men, were more likely to smoke and reported expecting greater satisfaction from smoking when they were told alcohol compared to told placebo. The effects of instruction condition on smoking behavior were not mediated by self-reported expected satisfaction from smoking.

Conclusions

Women may be more likely to choose to smoke after drinking moderate amounts of alcohol because of their expectations rather than the pharmacological effects of the alcohol.     

Effects of plant ingestion in rats determined by the conditioned taste aversion procedure

The conditioned taste aversion procedure was used to compare the aversive effects produced by 40 plants (mostly common household varieties) to those of amphetamine, lithium chloride and ethyl alcohol. Test substances (plant homogenates or drug solutions) were given to rats by force-feeding 5 min after the subjects' first exposure to 0·1% saccharin solution, which was available for 15 min from a water bottle. The comparison of the consumption of saccharin solution, two days after test substance administration, to the initial saccharin consumption was taken as a measure of the aversive effects produced by the test substance, e.g. greater suppression of saccharin intake indicating greater aversive properties. Dose dependent suppression of saccharin intake was obtained with most of the substances tested at more than one concentration. Administration of Pokeberry seeds, Japanese Yew, Norfolk Island Pine and Oleander leaves suppressed saccharin intake more than ethyl alcohol. The rest of the plants tested produced less conditioned aversion than ethyl alcohol. Some plants which are frequently called poisonous (Poinsettia, Philodendron and Dieffenbachia) were not particuarly effective in producing conditioned taste aversion. Good correlation existed between suppression of saccharin intake produced by the three drugs tested and their approximate acute lethal doses in rats and humans, suggesting that the conditioned taste aversion procedure may indicate the approximate acute lethality of these substances. Good correlation was also found between the dry weight of the plants and the suppression of saccharin intake.