Moderate Dose Of Ethanol Research Articles

Ethanol’s Effects on Operant Responding: Differentiating Reinforcement Efficacy and Motor Performance

PETRY, N. M. Ethanol’s effects on operant responding: Differentiating reinforcement efficacy and motor performance. Physiol Behav 64(1) 117–122, 1998. The purpose of this study was to examine the effects of ethanol on operant responding in rats. Drugs may affect response rates by several mechanisms, including altering motor performance or sensitivity to reinforcement. These two processes can be dissociated by applying a quantitative model of reinforced responding the response–strength equation, to response rates obtained during multiple variable-interval (VI) schedules of reinforcement. This equation has two fitted parameters. One ( k) is thought to measure changes in motor performance, and the other ( R e) is thought to measure changes in reinforcement efficacy. In experimental sessions, rats earned sucrose reinforcement on a seven-component multiple VI operant schedule. The average intervals varied from 108 to 3 s and provided reinforcement rates from 30 to 1200/h. Following stable baseline performance, rats were injected intraperitoneally prior to sessions with different doses of ethanol: 0.0, 0.3, 0.6, and 0.9 g/kg. Low to moderate doses of ethanol (0.3 and 0.6 g/kg) significantly decreased response rates on several of the VI schedules but did not alter either of the fitted parameters, suggesting that these doses of ethanol did not affect motor performance or sensitivity to reinforcement. The 0.9 g/kg dose decreased responding maintained by many of the VI schedules and significantly increased the R e parameter, suggesting that the sucrose became relatively less efficacious in ethanol compared to vehicle sessions. This relatively high dose of ethanol, however, did not alter responding maintained by the richest reinforcement schedule, and it did not affect motor performance as defined by the k parameter. These results suggest that, within this paradigm, ethanol affects motivation to respond rather than ability to respond.

Moderate and Large Doses of Ethanol Differentially Affect Hepatic Protein Metabolism in Humans ,

The intake of ∼70 g of alcohol impairs liver protein metabolism in healthy humans. To establish the threshold at which alcohol impairs hepatic protein metabolism in humans we compared the effects of 500 mL of water (control study), 300 (28.4 g ethanol) or 750 mL (71 g ethanol) of table wine on hepatic protein metabolism in three groups of healthy nonalcoholic volunteers. Hepatic protein metabolism was estimated (L-[1-14C]leucine infusion) by measuring the fractional secretory rates of albumin and fibrinogen during the overnight postabsorptive state (basal) and the subsequent administration of water or two different amounts of wine (300 or 750 mL) given with a liquid glucose-lipid-amino acid meal. During the meal, water did not affect fibrinogen fractional secretory rate and increased albumin fractional secretory rate by ∼50% (P < 0.01). The 300 mL of wine increased albumin secretory rate by only ∼20% (P < 0.01 vs. basal, P < 0.04 vs. water) and did not affect fibrinogen secretory rate. The 750 mL of wine profoundly impaired hepatic protein metabolism, decreasing the fractional secretory rates of albumin (P < 0.01 vs. water and 300 mL wine) and fibrinogen (P < 0.04 vs. water and 300 mL of wine) below the postabsorptive values. These results demonstrate that a moderate dose of alcohol (28 g, ∼2 drinks) slightly affects postprandial hepatic protein metabolism by blunting the meal-induced increase in albumin synthesis, whereas it does not interfere with fibrinogen synthesis as do higher doses.

Moderately high consumption of ethanol suppresses bone resorption in ovariectomized but not in sexually intact adult female rats.

Epidemiological studies suggest that moderate consumption of alcoholic beverages may be beneficial for bone in postmenopausal women. To investigate prospectively these uncontrolled observations, female rats were divided in four groups of 10 animals each and treated with 1) ovariectomy (OVX) and 2.5% ethanol diet (OVX-ETOH group), 2) OVX and control diet (OVX-C group), 3) sham surgery and 2.5% ethanol diet (SHAM-ETOH group), or 3) sham surgery and control diet (SHAM-C group). Three weeks after surgery, bone histomorphometry revealed that the OVX-C group, as expected, had lower trabecular bone volume and higher parameters of bone formation and resorption than the SHAM-C group (p < 0.01). Intake of ethanol did not change these parameters in the SHAM rats, but in the OVX rats it was associated with sharp reduction in parameters of bone resorption (p < 0.01) without a concomitant effect on parameters of bone formation. The cytokines are believed to contribute to accelerated bone resorption during the early postmenopausal period. Indeed, the peripheral blood monocytic cells (PBMC) from the OVX-C rats produced higher amounts of TNF-alpha than the PBMC from the SHAM-C rats (p < 0.05) and administration of ethanol prevented this increase in OVX rats but had no effect in SHAM rats. In summary, short-term intake of moderate doses of ethanol was associated with markedly different effects in rats with and without ovarian function. Although ethanol had no significant effect on the bone tissue and TNF-alpha production of the SHAM rats, it was associated with markedly lower parameters of bone resorption and less TNF-alpha production in the OVX animals. This suggests that exposure to low-dose ethanol may protect from osteopenia following cessation of ovarian function.

Ethanol consumption following recovery from unilateral damage to the forelimb area of the sensorimotor cortex: reinstatement of deficits and prevention of dendritic pruning

Unilateral injury to the forelimb-representation area of the sensorimotor cortex (FL-SMC) in adult rats results in use-dependent proliferation of dendritic processes, followed by partial pruning, of layer V pyramidal neurons of the contralateral homotopic cortex. In development, `exuberant' growth of neurons is often followed by pruning, a process that has been associated with a glutamatergic-NMDA receptor mechanism. A related mechanism may play a role in injury-related pruning of dendrites in adults. The N-methyl-d-aspartate (NMDA) receptor antagonist MK801, administered throughout the pruning phase to adult animals with FL-SMC lesions, prevents dendritic pruning and disrupts behavioral recovery. Ethanol (ETOH) also acts as an NMDA receptor antagonist. It has been shown to reduce NMDA-active ion currents, inhibit NMDA-evoked electrophysiological responses, and decrease glutamate-binding in the hippocampus and cortex. ETOH also affects neuromorphology in the developing and adult cerebellum, hippocampus, and cortex. Ethanol's involvement with NMDA receptor function and its influence on dendritic morphology led us to examine its effect on dendritic pruning and behavioral recovery following unilateral FL-SMC lesions. Lesioned animals were exposed to moderate doses of ethanol in a liquid diet only during the period of dendritic pruning. As with MK801, ETOH prevented pruning and reinstated chronic behavioral asymmetries.

Paradoxical effects of acute ethanolism in experimental brain injury.

Acute ethanol intoxication is a frequent complicating factor in human head injury, yet its impact on neurological outcome remains poorly defined. This study was undertaken to assess the effect of varying levels of preinjury ethanol on early postinjury mortality, recovery of motor function, and degree of neural degeneration after cortical contusion injury in the rat. Adult rats were pretrained on a beam-walking task, then randomized to one of five groups: low-dose ethanol and injury (1 g/kg, 16 animals); moderate-dose ethanol and injury (2.5 g/kg, 11 animals); high-dose ethanol and injury (3 g/kg, 17 animals); no ethanol and injury (nine animals); or ethanol and sham injury (seven animals). Forty minutes after intraperitoneal injection of ethanol or saline, the rats received a pneumatic piston-induced contusion injury of the left primary motor cortex. Their beam-walking ability was assessed daily for the next 7 days. At 4 weeks postinjury, the brains were sectioned and the dimensions of the cortical lesions were determined. Preinjury ethanol administration was associated with an acute postinjury mortality rate of 29.5% (p < 0.05); the highest mortality rate (47.1%) occurred in the high-dose ethanol group, whereas no deaths occurred in the animals in the no ethanol or sham-injured groups (p < 0.01). However, injured animals receiving low- and moderate-dose ethanol had significantly less severe beam-walking impairment initially, and a more rapid return to normal beam-walking ability, compared to the no and high-dose ethanol groups (p < 0.05). Additionally, the mean lesion volumes were significantly smaller in the low- and moderate-dose ethanol treatment groups compared to the no and high-dose ethanol groups (23.2 +/- 8 mm3 and 29 +/- 6.7 mm3 vs. 52 +/- 8.8 mm3 and 53.7 +/- 10.9 mm3, respectively, p < 0.01). In this cortical contusion model, the presence of ethanol before injury appears to exert a potent neuroprotective effect when administered in low or moderate doses. This action is postulated to result from ethanol-induced inhibition of N-methyl-D-aspartate receptor-mediated excitotoxicity. The loss of neuroprotection and increased mortality rates observed with high-dose ethanol may be related to ethanol-induced hemodynamic and respiratory depression.

Effect of ethanol on sustained attention in rats.

Acute exposure to ethanol produces deficits in sustained attention in humans, but these attentional deficits have not been modeled in animals. In this study, an operant task was used to investigate the effects of low and moderate doses of ethanol on sustained attention in rats. Performance on a two-choice reaction time task over a 1-h session was assessed immediately following administration of ethanol (0.0, 0.5, 0.75, 1.0 and 1.5 g/kg i.p.). Each rat was required to respond to a light stimulus of variable duration (20, 100, and 500 ms) occurring at one of two locations. Under control and saline conditions, increases in stimulus length systemically increased choice accuracy and decreased reaction time. Ethanol produced a dose-dependent decrease in choice accuracy that interacted with time, with an initial impairment that was stimulus length-dependent followed by a general vigilance decrement. The data demonstrate that ethanol impaired the ability of rats to direct and sustain attention to brief, infrequent stimuli, and provide a model for further investigations into the underlying neurobiological mechanisms for ethanol-induced attentional deficits.

Acute participant-rated and behavioral effects of alprazolam and buspirone, alone and in combination with ethanol, in normal volunteers.

The acute behavioral effects of buspirone (15 and 30 mg/70 kg), alprazolam (0.75 and 1.5 mg/70 kg), and placebo, alone and in combination with ethanol (0-0.6 g/kg), were tested in 13 volunteers. Ethanol alone produced only a few significant behavioral effects. Alprazolam and buspirone produced comparable dose-related increases in participant ratings of sedation, but only alprazolam impaired performance. The buspirone-ethanol and alprazolam-ethanol combinations produced robust sedative-like participant-related drug effects that were similar in magnitude, but, in general, only the alprazolam-ethanol combinations impaired performance. These findings suggest that the participant-rated effects of therapeutic doses of buspirone in combination with moderate doses of ethanol are similar to those of therapeutic doses of alprazolam in combination with ethanol, but the performance-impairing effects of buspirone are distinguishable from those of alprazolam, alone and in combination with ethanol.

Kinetic Interactions Between 4‐Methylpyrazole and Ethanol in Healthy Humans

4-Methylpyrazole (4-MP), a potent inhibitor of alcohol dehydrogenase activity, is a candidate to replace ethanol as the antidote for methanol and ethylene glycol intoxications, because it has a longer duration of action and apparently fewer adverse effects. To study a probable mutual inhibitory effect between ethanol and 4-MP on their elimination, two studies were performed in healthy human volunteers using double-blind crossover designs. In study A1 4-MP in the presumed therapeutic dose range of 10 to 20 mg/kg caused a 40% reduction in the rate of elimination of ethanol in 12 subjects given 0.5 to 0.7 g/kg of ethanol. These data suggest that such doses of 4-MP inhibit alcohol dehydrogenase activity in humans in vivo and would be effective at blocking methanol or ethylene glycol metabolism. In study B, ethanol (0.6 g/kg followed by 0.2 g/kg twice) significantly decreased the rate of elimination of 4-MP (5 mg/kg, given intravenously to four subjects). These moderate doses of ethanol also inhibited the rate of urinary excretion of 4-carboxypyrazole, the primary metabolite of 4-MP in humans. Data suggest that ethanol inhibits 4-MP metabolism, thereby increasing the duration of therapeutic blood levels of 4-MP in the body. This mutual interaction may have clinical implications, because most self-poisoned patients have also ingested ethanol. Theoretically, methanol and ethylene glycol might also show such interactions with 4-MP.

Cardiac Contractile and Sarcoplasmic Reticulum Function after Acute Ethanol Consumption

Since the contractile status of the myocardium depends on tight regulation of calcium concentration by the sarcoplasmic reticulum (SR), we investigated the possibility that acute ethanol-induced alterations in the calcium pump function of the SR could contribute to the myocardial depression seen after acute ethanol exposure. In this study, LV function (Langendorff preparation) was significantly reduced after ethanol (ETOH, 2.0 ml/kg, iv) in adult guinea pigs. Compared to control hearts (N= 10), hearts from ethanol-treated animals (N= 10) had significantly lower peak systolic LVP (84 ± 2 vs 67 ± 4 mmHg,P< 0.005), +dP/dt max (1175 ± 54 vs 967 ± 54 mmHg/sec,P< 0.02), and −dP/dt max (1087 ± 42 vs 892 ± 52 mmHg/sec,P< 0.02) and at a maximal isoproterenol dose of 30 ng/ml, had lower LVP (150 ± 5 vs 90 ± 6 mmHg,P< 0.02), +dP/dt max (3400 ± 120 vs 1800 ± 40 mmHg/sec,P= 0.001), and −dP/dt max (2500 ± 50 vs 1520 ± 40 mmHg/sec,P< 0.002) than control hearts. SR calcium ATPase activity was not altered by ethanol (control: 70.6 ± 2.6 μmol/mg protein/hr,N= 10; ETOH: 81.3 ± 6.9,N= 8). Maximal calcium uptake, however, was decreased 25% in SR vesicles isolated from ethanol-treated (3.8 ± 0.27 μmol/mg,N= 10) compared to control hearts (5.1 ± 0.20,N= 10,P< 0.01). Our data confirm that moderate doses of ethanol depress cardiac contractile function, and our finding that acute ethanol exposure decreased calcium uptake by the SR in the face of no change in calcium ATPase activity suggests that ethanol uncoupled ATP hydrolysis and calcium transport.

Metabolic mapping of the effects of chronic voluntary ethanol consumption in rats

The 2-[ 14C]deoxyglucose method was used to examine the effects of chronic, voluntary ethanol consumption on rates of local cerebral glucose utilization (LCGU). LCGU was measured in male Long-Evans rats immediately following the completion of a 60-min schedule-induced polydipsia drinking session. Three groups of animals were examined: animals with a history of ethanol consumption that received ethanol on the test day (ethanol-ethanol), animals with a similar ethanol history that were presented with water on the test day (ethanol-water), and a control group that received water throughout the experiment (water-water). Ethanol consumption on the test day resulted in a highly discrete pattern of metabolic changes, with significant decreases in glucose utilization in the hippocampal complex, habenula, anterior ventral thalamus, and mammillary bodies, whereas increases were observed in the nucleus accumbens and locus coeruleus. Rates of LCGU in the ethanol-water group were increased throughout all regions of the central nervous system examined, indicating that the long-term consumption of moderate ethanol doses that do not produce physical dependence can cause significant changes in functional brain activity.

Enhanced Sensitivity of Pituitary βEndorphin to Ethanol in Subjects at High Risk of Alcoholism

Previous studies have demonstrated that a moderate dose of ethanol induced a significant increase in the plasma beta-endorphin content of subjects from families with a history of alcoholism (high risk (HR)), but not subjects from families without a history of alcoholism (low risk (LR)). The objective of this study was to examine the response of the pituitary beta-endorphin and adrenal cortisol systems to various concentrations of ethanol in male and female subjects at high and low risk of the future development of alcoholism. All subjects participated in four experimental sessions. In each session the subjects were given a drink containing one of the following doses of ethanol: 0, 0.25, 0.50, and 0.75 g of ethanol per kilogram of body weight (for a 60- to 70-kg individual). Blood samples were taken at 0 minutes and at 15, 45, 120, and 180 minutes after the drink for estimation of the blood alcohol, plasma beta-endorphin, and plasma cortisol levels. The concentration of alcohol in the blood at various intervals after the drink was similar among the subjects, regardless of the risk group. Ethanol increased the plasma level of beta-endorphin-related peptides of the HR but not of the LR subjects in a dose-dependent manner. All subjects showed a small decrease in plasma cortisol level with time, but ethanol ingestion did not significantly alter the plasma cortisol levels. This study indicates that the pituitary beta-endorphin system, but not the adrenal cortisol system, of the HR subjects shows an enhanced sensitivity to ethanol, which may be an important factor in controlling ethanol consumption.

MEASURING AND REPORTING THE CONCENTRATION OF ACETALDEHYDE IN HUMAN BREATH

Most of the acetaldehyde generated during the metabolism of ethanol becomes tightly bound to endogenous molecules such as haemoglobin, amino acids and certain phospholipids. Free acetaldehyde passes the blood-brain barrier and traces of this toxic metabolite are excreted through the lungs and can be detected in the expired air. The blood/air partition coefficient of acetaldehyde at 34 degrees C, the average temperature of end-expired air, is about 190:1. Because of various problems associated with measuring acetaldehyde in blood samples, several research groups have instead investigated the analysis of acetaldehyde in breath which offers an indirect and alternative approach for clinical and research purposes. However, care is needed when interpreting the results of breath acetaldehyde measurements, because of the possibility of local formation from microflora inhabiting the upper airways and mouth. The concentration of acetaldehyde exhaled in breath after drinking alcohol demonstrates large inter-individual differences depending on various genetic (racial) and environmental factors. Moreover, acetaldehyde is an endogenous metabolite and even without drinking any alcohol the concentrations expelled in breath span from 0.2 to 0.6 nmol/l, with higher levels observed in smokers and abstinent alcoholics. Breath acetaldehyde concentration reached between 5 and 50 nmol/l in European subjects who drank a moderate dose of ethanol (0.4-0.8 g/kg), with the highest values seen in smokers. The concentration of breath acetaldehyde in Japanese subjects after drinking alcohol reached between 200 and 500 nmol/l at the peak. These much higher levels follow because a large proportion of Orientals (40-50%) inherit an inactive form of the low Km mitochondrial isoenzyme of aldehyde dehydrogenase (ALDH2). The highest concentration of breath acetaldehyde were seen in healthy Caucasians who drank a small dose of alcohol (0.25 g/kg) after taking the alcohol-sensitizing drug calcium carbimide, which blocks the action of ALDH isozymes. During the most intense acetaldehyde-flush reaction, breath acetaldehyde reached between 200 and 1300 nmol/l, but even these abnormally high concentrations did not interfere with the analysis of ethanol in breath by means of non-specific infrared analysers currently used in many countries for testing drinking drivers.

Alcohol and human emotion: A multidimensional analysis incorporating startle-probe methodology.

The effect of alcohol intoxication on emotional response was investigated using a model of emotion that includes both arousal and valence dimensions. Thirty-six university students were exposed to multiple presentations of photographic slides selected to elicit distinctive emotional reactions ranging from very pleasant to very unpleasant; half of them received a moderate (approximately .75 ml/kg) dose of ethanol. The students' psychophysiological responses indicated that both general startle reactivity and autonomic indices specific to emotional arousal were diminished by alcohol. However, the affective modulation of startle, occurring with emotional states manipulated by slides with distinct valences, remained intact. These findings suggest that stress-response dampening by alcohol may involve a nonspecific attenuation of arousal reactions evident for positive as well as negative stimuli and that theories of motivation for drinking that are based on mood alteration may need refinement. Language: en

Alcohol and human emotion: a multidimensional analysis incorporating startle-probe methodology.

The effect of alcohol intoxication on emotional response was investigated using a model of emotion that includes both arousal and valence dimensions. Thirty-six university students were exposed to multiple presentations of photographic slides selected to elicit distinctive emotional reactions ranging from very pleasant to very unpleasant; half of them received a moderate (approximately .75 ml/kg) dose of ethanol. The students' psychophysiological responses indicated that both general startle reactivity and autonomic indices specific to emotional arousal were diminished by alcohol. However, the affective modulation of startle, occurring with emotional states manipulated by slides with distinct valences, remained intact. These findings suggest that "stress-response dampening" by alcohol may involve a nonspecific attenuation of arousal reactions evident for positive as well as negative stimuli and that theories of motivation for drinking that are based on mood alteration may need refinement.

Effects of chronic alcohol on immunoreactive beta-endorphin secretion from hypothalamic neurons in primary cultures: evidence for alcohol tolerance, withdrawal, and sensitization responses.

Endogenous opioid peptides are known to be involved in the alcohol tolerance and dependence following alcohol abuse. However, the cellular mechanisms involved in the ethanol tolerance and dependence are not well established. We have previously shown that low concentrations of ethanol stimulate immunoreactive beta-endorphin (IR-beta-EP) release from the cultured hypothalamic neurons and that chronic ethanol exposure desensitizes these neurons to ethanol challenges. In this study, we determined the IR-beta-EP response to increasing doses of ethanol during the desensitizing phase of moderate ethanol doses to test whether the cultured IR-beta-EP-secreting neurons develop tolerance to ethanol following constant exposure. We also determined IR-beta-EP responses following withdrawal from chronic ethanol challenge and compared the IR-beta-EP secretory response to various doses of ethanol in ethanol-naive and ethanol-preexposed cultures. The IR-beta-EP responses to increasing doses of ethanol (50-150 mM) were markedly reduced in the cultures preexposed to a 50 mM dose of ethanol when compared with those that were naive to ethanol. The ethanol-exposed cultures showed hypersecretion of IR-beta-EP after removal from 48 hr of constant ethanol, as compared with ethanol-naive cultures. When ethanol-preexposed cultures were challenged with various doses of ethanol 4 days after ethanol withdrawal, the cultures showed higher IR-beta-EP secretory responses than did the ethanol-naive cultures. These data suggest that IR-beta-EP secretory neurons in primary cultures develop tolerance to chronic ethanol, show withdrawal response after removal of chronic ethanol exposure, and develop sensitization following repeated ethanol challenges.

Ethanol attenuation of ganglioside sialylation and neuritogenesis

Neurite-producing cultured embryonic chick brain neurons in 96-h culture were exposed chronically to 25 mM ethanol for a 72-h period. Neurital plasma membrane extension was markedly attenuated in the ethanol-exposed neurons as compared with ethanol-free control cultures. The rate of biosynthetic sialylation of gangliosides, which are major structural sialoglycosphingolipid components in the exofacial lipid bilayer of the neurital plasma membrane, decreased to about half that in the alcohol-free neurons. The findings show that ganglioside sialylation in the morphodifferentiating central nervous system neuron is significantly attenuated by chronic exposure to a moderate dose of ethanol. Depression of ganglioside-dependent neuritogenesis may represent a mechanism for development of the central nervous system component of the fetal alcohol syndrome.

Phenotypic characterization of second generation offspring of alcohol-sensitive ANT and alcohol-insensitive AT rat lines

The alcohol-sensitive ANT and the alcohol-insensitive AT rat lines developed by selective breeding for differential sensitivity to motor impairment on the tilting plane by a moderate ethanol dose (2 g/kg, IP), were cross-bred to produce second generation (F 2) offspring to study phenotypic correlations between various behavioral and biochemical properties and the degree of initial alcohol sensitivity in the tilting plane test. The F 2 population ( n = 75) was subjected to alcohol sensitivity tests using a tilting plane test and a sleep time test, and to the elevated plus-maze test of sober activity and anxiety. Finally, the animals were sacrificed and the concentrations of dopamine and its acidic metabolites were analyzed in their striatal tissues. Serum corticosterone was determined to obtain information about the stress responses of the animals after the tilting plane test. The behaviors studied had no significant correlations with each other, suggesting that the various genetic and environmental factors affecting these behavioral phenotypes are different for each behavior. The biochemical measures yielded some correlations with the tilting plane test results that were contrary to the differences between the parent rat lines (dopaminergic indices) or that were confounded by the correlations with the body weight of the animals (corticosterone). Body-weight independent correlational tendency between the alcohol-induced impairment in motor performance and serum corticosterone concentration, however, fitted the differences between the parent lines, suggesting that stress mechanisms cannot be fully excluded as factors contributing to the differential alcohol sensitivity between the ANT and AT rat lines.

Effects of ondansetron pretreatment on acute responses to ethanol in social drinkers.

Laboratory animal and clinical studies suggest that the 5-HT(3) receptor subtype may mediate some of the CNS effects of ethanol. Two experiments were conducted to evaluate the effects of the 5-HT(3) receptor antagonist, ondansetron, on the acute responses of social drinkers to a moderate dose of ethanol. In Experiment 1, two doses of ondansetron (0.15 and 0.30mg) or placebo were tested in combination with ethanol (0.5g/kg) or placebo. In Experiment 2, three higher doses of ondansetron (1.0, 3.0 and 10.0mg) or placebo were tested in combination with ethanol (0.5g/kg) or placebo. Sessions were conducted one or two evenings per week from 16.00h until 20.45h. Separate groups of subjects participated in the two placebo-controlled, double-blind experiments (Experiment 1: n = 13; Experiment 2: n = 6). The order of drug administration was counterbalanced across subjects. In each study, subjects were given an intravenous infusion of ondansetron and 5min later consumed an ethanol or placebo beverage. For 3h after the beverage was consumed, physiological, subjective effects and performance measures were taken at regular intervals. Across a wide range of doses, the effects of ondansetron alone did not differ significantly from placebo. Ethanol alone produced prototypic effects on several measures (e.g., increased ratings of "positive" subjective effects and impaired memory performance). Furthermore, ondansetron pretreatment did not modify physiological, subjective or performance effects of ethanol. These findings do not support the hypothesis that the 5-HT(3), receptor/channel complex mediates the positive subjective effects, or any other subjective or performance effects, of ethanol.

Low and moderate doses of ethanol produce distinct patterns of cerebral metabolic changes in rats.

The quantitative autoradiographic 2-[14C]deoxyglucose method was used to measure the effects of the acute administration of ethanol on local rates of glucose utilization in male Sprague-Dawley rats. Rates of glucose utilization were measured 10 min after the intraperitoneal administration of 0.00, 0.25, 0.50, and 1.00 g/kg ethanol. The acute administration of the lowest dose of ethanol (0.25 g/kg) significantly increased rates of cerebral metabolism, as compared with vehicle-treated controls, in structures of the mesocorticolimbic and nigrostriatal dopaminergic systems. Among the affected regions were the nucleus accumbens, medial prefrontal cortex, olfactory tubercle, caudate, ventral tegmental area, and substantia nigra. Acute administration of 0.50 g/kg ethanol resulted in similar trends in increased functional activity; however, significant increases were limited to the somatosensory cortex, posterior nucleus accumbens, and the CA3 region of the hippocampus. In contrast, the administration of 1.00 g/kg ethanol produced widespread decreases in rates of glucose utilization in brain regions involved in processing of sensory and motor information, as well as in portions of the limbic system. These data indicate that the effects of acute ethanol administration on functional activity as reflected by rates of glucose utilization are dose-dependent. These cerebral metabolic effects parallel the dose-dependent effects of ethanol on motor behavior, with stimulatory effects generally observed at lower doses and depressive effects at higher doses. Moreover, each of the doses studied produced alterations in functional activity in a unique subset of structures. This suggests that different neuroanatomical circuits mediate the effects of each dose.

Acute Alcohol Intake Decreases Short-Term Heart Rate Variability in Healthy Subjects

1. The acute effects of a moderate dose of ethanol (1g/kg body weight) on heart rate and blood pressure variability and baroreflex sensitivity were studied in 12 healthy male subjects in a juice-controlled experiment. Electrocardiographic and finger blood pressure data were recorded and stored in a minicomputer during 5 min of controlled breathing (15 cycles/min) and during deep breathing (5 s inspiration, 5 s expiration, four cycles) before drinking and hourly thereafter for 3 h. 2. Mean breath alcohol concentration rose to 18.9 mg/100 ml. In the time domain analysis, the root mean square difference of successive R-R interval decreased significantly with ethanol as compared with the juice experiment. The difference remained statistically significant even after adjustment for the shorter R-R interval after alcohol. In the frequency domain analysis the high-frequency (0.15-0.5 Hz) spectral power showed a significant decrease after alcohol intake. Also, the index of sensitivity of the baroreceptor reflex (square root of R-R interval power/systolic blood pressure power) decreased significantly in the high-frequency component. Ethanol did not change finger systolic blood pressure, and power spectral analysis did not show significant variability in blood pressure. 3. These data indicate that acute intake of moderate amounts of alcohol causes a significant decrease in heart rate variability owing to diminished vagal modulation of the heart rate.