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PubMed2005

Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome.

OBJECTIVE: Prenatal alcohol exposure results in fetal death and neurobehavioral complications including learning impairment. Previously synthetic peptides derived from activity-dependent neurotrophic factor have been shown to prevent aspects of alcohol-induced damage in pregnancy. The objective of this work was to evaluate whether activity-dependent neurotrophic factor-12 could prevent alcohol-induced damage in a model of fetal alcohol syndrome. STUDY DESIGN: Using a well-characterized model, C57Bl6/J mice on gestational day 8 were treated with placebo, alcohol (30% volume/volume alcohol 0.03 mL/kg), alcohol plus activity-dependent neurotrophic factor-12 30 minutes prior to alcohol, or activity-dependent neurotrophic factor-12 alone. Fetal death was assessed on gestational day 18 (25 litters were evaluated: alcohol, n = 5; placebo, n = 9; alcohol plus activity-dependent neurotrophic factor-12, n = 11). Neonatal behavior tests were performed on postnatal days 1 through 21 with the offspring of 12 dams (alcohol, n = 16; placebo, n = 46; alcohol plus activity-dependent neurotrophic factor-12, n = 23; and activity-dependent neurotrophic factor-12, n = 35). Adult males were tested in the Morris water maze for learning assessment and with the hole punch activity test for exploratory activity. Statistical analysis included Kruskal-Wallis and analysis of variance. RESULTS: Fetal death was greater in alcohol (67% +/- 13%) vs placebo (8.4% +/- 3%, P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced fetal death (2.2% +/- 8.1%) with levels similar to control (P = .12). Alcohol exposure caused a delay in achieving developmental milestones, with alcohol achieving milestones later than all other groups (all P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced milestone delays. In the Morris water maze, the placebo learned, decreasing their latency to find the hidden platform over 70% (P < .01). Alcohol plus activity-dependent neurotrophic factor-12 also significantly learned, with a learning curve not different from placebo (all P > .5) and significantly better than alcohol on days 4, 6, and 7 (all P < .05). Alcohol exposure resulted in significantly less time in hole punch activity (P < .02) than control. Activity-dependent neurotrophic factor-12 pretreatment prevented the alcohol-induced decline, with levels the same as control (P = .1). CONCLUSION: The novel peptide activity-dependent neurotrophic factor-12 prevents alcohol-induced fetal death and developmental and learning abnormalities in a model of fetal alcohol syndrome. This demonstrates that a single treatment with a peptide is efficacious and may be of value in the prevention of alcohol-induced damage.

Animals↗
PubMed2001

Induction of steady-state blood alcohol levels: application to the study of within-session alcohol tolerance in rats.

BACKGROUND: The study of within-session alcohol tolerance in the rat has been hampered by methodological difficulties related to the measurement of dependent variables at predictable blood alcohol concentrations (BAC) during a single session of alcohol exposure. This study characterizes a method for maintaining steady-state blood alcohol levels over several hours in the rat, referred to as the "alcohol clamp." METHODS: Wistar rats were implanted with an indwelling catheter in the carotid artery for blood sampling and another in the external jugular vein for alcohol infusion. To clamp BAC at a predetermined level, rats first were infused with a priming dose of alcohol to establish the desired or "target" BAC, followed by a continuous infusion of alcohol at a rate equal to that of alcohol metabolism in the rat. This maintained BAC at a constant level over time. BACs of 100, 200, or 300 mg% were maintained over several hours in separate groups of rats. The alcohol clamp was applied to the study of acute (within-session) alcohol tolerance in rats selectively bred for high and low alcohol drinking. Alcohol-induced hypothermia was used to index tolerance, and within-session alcohol tolerance was defined as a return of body temperature toward baseline during the course of the alcohol infusion while BAC was maintained at a constant level. RESULTS: The continuous alcohol infusion procedure maintained BAC in a steady state throughout the 3 hr alcohol infusion session at each of the three target BAC levels. Alcohol infusion induced a drop in body temperature, followed by a return of temperature toward baseline during the course of infusion, which indicated the development of within-session alcohol tolerance. CONCLUSIONS: The continuous alcohol infusion procedure (alcohol clamp) maintained BAC in a steady state, both within and between subjects, across a wide range of blood alcohol levels. The alcohol clamp appears to be a useful tool for subsequent studies of within-session alcohol tolerance in the rat.

Alcohol Drinking↗
PubMed2003

Alcohol consumption and liver cirrhosis mortality with and without mention of alcohol--the case of Canada.

AIMS: To analyse post-war variations in per capita alcohol consumption in relation to gender-specific liver cirrhosis mortality in Canadian provinces and to assess the extent to which alcohol bears a different relation to cirrhosis deaths with mention of alcohol (alcoholic cirrhosis) compared to cirrhosis deaths without mention of alcohol (non-alcoholic cirrhosis). DATA AND METHOD: Annual liver cirrhosis mortality rates by 5-year age groups were converted into gender-specific and age-adjusted mortality rates. Outcome measures included total cirrhosis-the conventional measure of liver cirrhosis--alcoholic cirrhosis and non-alcoholic cirrhosis. Per capita alcohol consumption was measured by alcohol sales and weighted with a 10-year distributed lag model. A graphical analysis was used to examine the regional relationship and the Box-Jenkins technique for time-series analysis was used to estimate the temporal relationship. FINDINGS: Geographical variations in alcohol consumption corresponded to variations in total liver cirrhosis and particularly alcoholic cirrhosis, whereas non-alcoholic cirrhosis rates were not associated geographically with alcohol consumption. In general, for all provinces, time-series analyses revealed positive and statistically significant effects of changes in alcohol consumption on cirrhosis mortality. In Canada at large, a 1-litre increase in per capita consumption was associated with a 17% increase in male total cirrhosis rates and a 13% increase in female total cirrhosis rates. Alcohol consumption had a stronger impact on alcoholic cirrhosis, which increased by fully 30% per litre increase in alcohol per capita for men and women. Although the effect on the non-alcoholic cirrhosis rate was weaker (12% for men and 7% for women) it was nevertheless statistically significant and suggests that a large proportion of these deaths may actually be alcohol-related. CONCLUSIONS: Some well-established findings in alcohol research were confirmed by the Canadian experience: per capita alcohol consumption is related closely to death rates from liver cirrhosis and alcohol-related deaths tend to be under-reported in mortality statistics.

Alcohol Drinking↗
PubMed2006

Environmental cues, alcohol seeking, and consumption in baboons: effects of response requirement and duration of alcohol abstinence.

BACKGROUND: Environmental stimuli (cues) that have been paired with alcohol drinking may evoke classically conditioned states that in turn influence alcohol consumption and relapse to heavy drinking. Animal models using chained schedules of alcohol reinforcement may be useful for examining such complex interactions. METHODS: Alcohol drinking was established in 4 baboons. A sequence of lights and tones was presented during daily 3-hour sessions. First, cues were presented alone and no programmed contingencies were in effect. Second, cues were paired with 3 linked components consisting of different behavioral contingencies leading to and concluding with access to alcohol for self-administration in the last component (i.e., a chained schedule of alcohol reinforcement). Third, the effects of withholding alcohol access (i.e., forced abstinence) and increasing the number of lever responses required per drink were evaluated. RESULTS: Cues paired with a chained schedule of alcohol reinforcement engendered behaviors that brought baboons into contact with alcohol-related cues and occasioned operant responding that facilitated access to alcohol (alcohol seeking) during components that preceded alcohol access. Increasing the response requirement for each drink decreased the number of drinks and volume of alcohol consumed, but did not alter alcohol seeking. On the first session after 14 days of alcohol abstinence, latency to complete the operant requirement that produced alcohol access was decreased while both alcohol self-administration and volume of alcohol consumed were increased. CONCLUSIONS: Alcohol self-administration and consumption were sensitive to increases in response requirement and duration of alcohol abstinence, while seeking was only enhanced by duration of alcohol abstinence. This animal model may be useful to further examine the interactions between environmental cues and behaviors associated with seeking and consumption of alcohol and to evaluate the efficacy of potential alcohol treatment drugs on these behaviors.

Alcohol Drinking↗
PubMed2006

Physiological and subjective responding to alcohol cue exposure in alcoholics and control subjects: evidence for appetitive responding.

36 alcoholic patients, recruited from a treatment program, and 20 non-alcohol abusing control subjects were tested for their reactions to alcohol and non-alcohol cues. The cue exposure paradigm included audio-visual (video), tactile, olfactory, and guided imagery cue components related to alcohol and non-alcohol beverages. Response measures were analyzed for significant difference based on alcohol and non-alcohol cue and patient type. Among the subjective ratings, alcohol cue specific increases in alcohol craving, desire to drink, alcohol-like high, positive drinking expectancies and alcohol-like withdrawal were seen in alcoholic subjects. Among the physiological measures, alcohol cue specific increases in salivation were seen in alcoholic subjects. Changes in heart rate, skin conductance and temperature were not specific to alcohol cues, or to alcoholic patients. The smelling of alcohol had the greatest impact on alcohol craving and skin conductance in alcoholic subjects. These findings demonstrate robust subjective effects, and weak physiological effects, in response to a multidimensional alcohol cue exposure paradigm. The response profile indicates cue reactivity in alcoholics as an appetitive based form of alcohol craving.

Adult↗
PubMed1999

Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk.

BACKGROUND: Substantial evidence exists for an important genetic contribution to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs. METHODS: Telephone interview follow-up data were obtained on twins from male, female and unlike-sex twin pairs who had participated in an alcohol challenge study in 1979-81, as well as other pairs from the same Australian twin panel surveyed by mail in 1980-82. RESULTS: At follow-up, alcohol challenge men did not differ from other male twins from the same age cohort on measures of lifetime psychopathology or drinking habits; but alcohol challenge omen were on average heavier drinkers than other women. A composite alcohol sensitivity measure, combining subjective intoxication and increase in body-sway after alcohol challenge in 1979-81, exhibited high heritability (60 %). Parental alcoholism history was weakly associated with decreased alcohol sensitivity in women, but not after adjustment for baseline drinking history, or in men. High alcohol sensitivity in men was associated with substantially reduced alcohol dependence risk (OR = 0.05, 95% CI 0.01-0.39). Furthermore, significantly decreased (i.e. low) alcohol sensitivity was observed in non-alcoholic males whose MZ co-twin had a history of alcohol dependence, compared to other non-alcoholics. These associations remained significant in conservative analyses that controlled for respondents' alcohol consumption levels and alcohol problems in 1979-81. CONCLUSIONS: Men (but not women) at increased genetic risk of alcohol dependence (assessed by MZ co-twin's history of alcohol dependence) exhibited reduced alcohol sensitivity. Associations with parental alcoholism were inconsistent.

Adult↗
PubMed2003

A comparative study on alcohol-preferring rat lines: effects of deprivation and stress phases on voluntary alcohol intake.

BACKGROUND: Voluntary alcohol intake in rats can be influenced by alcohol deprivation phases and stress. We investigated the magnitude of the effects of both deprivation and stress (forced swimming in cold water and foot-shock had been chosen as stressors distinct in their physical and psychological features) on alcohol intake and the influence of these experiences on the time course of alcohol drinking behavior. For the alcohol drinking procedure, a long-term model of alcohol self-administration originally developed for heterogeneous Wistar rats was used and was compared with different alcohol-preferring rat lines. METHODS: Adult male Alko alcohol (AA), alcohol-preferring (P), high-alcohol-drinking (HAD), and unselected Wistar rats were given ad libitum access to water, 5%, and 20% alcohol solutions for 6 months. A deprivation phase of 14 days was performed after 8 weeks of access to alcohol. After 16 weeks and 22 weeks of alcohol access, all animals were subjected to forced swimming and foot-shock, respectively, for 3 consecutive days, while alcohol intake was still being measured. RESULTS: Alcohol deprivation led to a significant increase in alcohol intake in Wistar rats and P rats. No alcohol deprivation effect was observed in HAD and AA rats; after deprivation, however, their preference for the 20% alcohol solution increased, immediately in the HAD rats and gradually over time in the AA rats. Repeated swim stress caused an increase in alcohol intake in Wistar rats but no changes in the alcohol-preferring rat lines. Foot-shock stress increased alcohol consumption in all lines of rats, but the most pronounced effects were observed in HAD and P rats. CONCLUSIONS: Wistar, HAD, P, and AA rats differentially respond to alcohol deprivation and stress, showing that the genetic background of these different rat lines profoundly affects relapse-like drinking and stress-induced drinking.

Alcohol Drinking↗
PubMed2000

Alcoholics' selective attention to alcohol stimuli: automated processing?

OBJECTIVE: This study investigated alcoholics' selective attention to alcohol words in a version of the Stroop color-naming task. METHOD: Alcoholic subjects (n = 23) and nonalcoholic control subjects (n = 23) identified the color of Stroop versions of alcohol, emotional, neutral and color words. Manual reaction times (RTs), skin conductance responses (SCRs) and heart rate (HR) were recorded. RESULTS: Alcoholics showed overall longer RTs than controls while both groups were slower in responding to the incongruent color words than to the other words. Alcoholics showed longer RTs to both alcohol (1522.7 milliseconds [ms]) and emotional words (1523.7 ms) than to neutral words (1450.8 ms) which suggests that the content of these words interfered with the ability to attend to the color of the words. There was also a negative correlation (r = -.41) between RT and response accuracy to alcohol words for the alcoholics, reflecting that the longer time the alcoholics used to respond to the color of the alcohol words, the more incorrect their responses were. The alcoholics also showed significantly greater SCRs to alcohol words (0.16 microSiemens) than to any of the other words (ranging from 0.04-0.08 microSiemens), probably reflecting the emotional significance of the alcohol words. Finally, the alcoholics evidenced smaller HR acceleration to alcohol (1.9 delta bpm) compared to neutral (2.8 delta bpm), which could be related to difficulties alcoholics experience in terminating their attention to the alcohol words. CONCLUSIONS: These findings indicate that it is difficult for alcoholics to regulate their attention to alcohol stimuli, suggesting that alcoholics' processing of alcohol information is automated.

Adult↗
PubMed2005

Alcohol cue reactivity in alcohol-dependent adolescents.

OBJECTIVE: There is substantial evidence that adults with alcohol dependence show different responses (increased craving, increased salivation, changes in heart rate) to alcohol-related stimuli (i.e., alcohol cue reactivity) than nonalcoholics. Alcohol cue reactivity appears to be related to dependence severity and has been used to predict treatment outcomes, where more reactive alcoholics have poorer outcomes than less reactive alcoholics. Adolescents may also develop alcohol dependence, though it is uncertain whether they experience craving and cue reactivity in the presence of alcohol-associated stimuli. METHOD: To examine whether adolescents with alcohol dependence show alcohol cue reactivity, 28 alcoholic adolescents and 25 nonalcoholic adolescents (ages 14-19 years) were compared using a standard cue reactivity procedure, where participants view, hold and sniff different beverages, one of which is their preferred alcoholic beverage. Cue reactivity was assessed with subjective craving ratings, salivation (grams), and heart rate (beats per minute). Analyses were conducted by covarying response to control beverages. RESULTS: Alcoholics responded with both greater craving and greater salivation to the alcohol cue (controlling for response to control cues) than did nonalcoholics, supporting the hypothesis that adolescent alcoholics show alcohol cue reactivity. Heart rate showed no differential cue effect between alcoholics and controls. CONCLUSIONS: Findings support that adolescent alcoholics experience alcohol cue reactivity, as evidenced by increased salivation and subjective craving in the presence of alcohol-related stimuli. Investigation of treatments that may reduce alcohol craving and cue reactivity in adolescents with alcohol dependence is warranted.

Adolescent↗
PubMed1988

Reliability and validity of the quantitative inventory of alcohol disorders (QIAD) and the veracity of self-report by alcoholics.

The purpose of this study was to investigate a recently developed instrument for alcoholism severity: The Quantitative Inventory of Alcohol Disorders (QIAD). The primary intention was to demonstrate the reliability and validity of the QIAD as a diagnostic tool within the field of alcoholism. A secondary intention was to examine the veracity of alcoholics self-report on the QIAD and other alcohol-related instruments. The subjects for the experimental group were 25 inpatient alcoholics and their spouses. The control group consisted of 21 nonalcoholics and their spouses. All subjects were administered the QIAD, Michigan Alcoholism Screening Test (MAST), and the Alcohol Severity Rating Scale (ASRS). The alcoholics and partners were given the same tests 5 to 8 days after initial testing. The primary therapists for the alcoholics were asked to rate alcoholism severity for each subject using the ASRS. Pearson product moment correlation coefficients were used for the test-retest reliability procedure. Alcoholics scores on the QIAD, MAST, and ASRS were compared with their spouses scores using a test-retest procedure. Nonalcoholics scores on these instruments were also compared with their spouses' scores. Construct and concurrent validity for the QIAD were tested through comparison of QIAD scores of the alcoholics with their corresponding scores on the MAST and ASRS. t-Tests were used to determine differences between alcoholics and nonalcoholics on all three scales. The results of this investigation supported the position that the QIAD is a reliable and valid instrument for measuring alcoholism severity. The QIAD correlated highly for both the alcoholics and their spouses. The test-retest procedure revealed a high level of correlation. A significant difference was found between the QIAD scores of the alcoholics and nonalcoholics. Construct validity was demonstrated by significant correlations between the alcoholics QIAD and MAST scores, both measuring the extent of alcoholism. The QIAD demonstrated concurrent validity by significantly correlating with alcoholics ASRS ratings. High correlations between alcoholic and spouse scores on the QIAD supported the hypothesis that inpatient alcoholics can produce valid responses to self-report questionnaires.

Adult↗
PubMed2002

Inverse genetic association between alcohol preference and severity of alcohol withdrawal in two sets of rat lines selected for the same phenotype.

BACKGROUND: The purpose of the present study was to determine whether alcohol-naïve rats selectively bred for alcohol preference or nonpreference differ in alcohol withdrawal severity using two sets of rat lines selectively bred for the same phenotype. METHODS: Alcohol-naïve male rats from the high alcohol drinking (HAD1) and low alcohol drinking (LAD1) rat lines and from the alcohol preferring (P) and nonpreferring (NP) rat lines received an intragastric infusion of alcohol (4.0 g/20.3 ml/kg; 25% v/v) or an equal volume of water once a day for 10 consecutive days. Alcohol withdrawal severity was assessed at using a behavioral rating scale and a radiant heat assay measured analgesia at 10, 12, 14, 16, 18, and 24 hrs following infusion of alcohol or water on days 1, 5, and 10 of treatment. RESULTS: Data were analyzed using body weight as a co-factor to correct for differences in body weight between the HAD1/LAD1 and P/NP lines. Acute (1 day) but not repeated alcohol treatment (5 or 10 days) produced mild behavioral signs of withdrawal in LAD1 but not in HAD1 rats. HAD1 and LAD1 rats showed alcohol-induced analgesia after 1 and 5 days of alcohol treatment that disappeared by day 10 in both lines. Repeated alcohol treatment (5 days) produced mild behavioral signs of withdrawal in NP but not in P rats. Neither P nor NP rats showed alcohol-induced analgesia after 1, 5, or 10 days of alcohol treatment. CONCLUSIONS: An inverse genetic association was found between alcohol preference and severity of alcohol withdrawal in two sets of rat lines selected for the same phenotype. The pattern of alcohol withdrawal that emerged over the course of the 10 days of alcohol treatment differed between the two lines selected for low alcohol drinking (LAD1 and NP), suggesting that unique sets of genes may influence alcohol withdrawal severity in the two lines.

Alcohol Drinking↗
PubMed1988

Patterns of familial alcoholism, alcoholism severity, and psychopathology.

The interrelationships among the severity of alcoholism, psychopathology/personality, and the degree of familial alcoholism were examined using the following four familial alcoholism classification schemes, which each differentiated three degrees of familial alcoholism: 1) conventional, compared alcoholics with no, nonparental, and parental alcoholic relatives; 2) lineality, distinguished between subgroups with alcoholism in neither, one, or both sides of their family; 3) generational, compared alcoholics having no, one, or two generations of familial alcoholism; 4) quantitative, credited one point for each first-degree and 1/2 point for each second-degree alcoholic relative. The subjects were 83 male alcoholic Veterans Administration inpatients 50 years of age or under. The Alcohol Use Inventory, various alcohol-related symptoms and behaviors, and laboratory values were used to evaluate the severity/pattern of alcoholism. Psychopathology/personality were measured by the MMPI, the Psychopathic State Inventory, the MacAndrew Alcoholism Scale, the Childhood Problem Behaviors Questionnaire, and the percentage of patients with an antisocial personality disorder (ASP) diagnosis. Surprisingly few subgroup differences were revealed in the severity/pattern of alcoholism. Only age at time of treatment and use of nonalcoholic drugs were associated with increasing familial alcoholism. On the other hand, childhood behavior problems, particularly antisocial behavior, and an ASP diagnosis were found to be associated with an increasing degree of familial alcoholism. The diagnosis of ASP was most apparent in the two-generational and bilineal alcoholics, while an increased degree of familial alcoholism was not associated with ASP for the conventional classification. Bilineal familial alcoholics also exhibited an MMPI profile reflective of a characterological disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Further evidence of an inverse genetic relationship between innate differences in alcohol preference and alcohol withdrawal magnitude in multiple selectively bred rat lines.

BACKGROUND: We have previously shown that a genetic association exists between low alcohol drinking and high alcohol withdrawal magnitude after acute alcohol exposure in alcohol-naïve rats. However, the behavioral rating scale used in this prior study was not optimal for assessing the magnitude of mild alcohol withdrawal. The present study examined whether a genetic relationship is again found between alcohol preference and alcohol withdrawal magnitude when a sensitive measure is used to index mild alcohol withdrawal in rats. METHODS: Alcohol-naïve, male rats selectively bred for alcohol preference (P, HAD1, HAD2) or nonpreference (NP, LAD1, LAD2) received a single intragastric infusion of alcohol (4.0 g/20.3 ml/kg body weight; 25% v/v) or water followed by acoustic startle testing. RESULTS: Startle probability and magnitude was greater in water-treated P than in water-treated NP rats. During alcohol withdrawal, startle probability and magnitude was suppressed in P rats and elevated in NP rats relative to water-treated controls. Startle probability and magnitude was greater in water-treated LAD1 rats than in water-treated HAD1 rats. During alcohol withdrawal, startle probability and magnitude was suppressed in HAD1 and elevated in LAD1 rats relative to water-treated controls at 20 hr after acute alcohol exposure. Startle probability and magnitude did not differ between water-treated HAD2 and water-treated LAD2 rats. During alcohol withdrawal, there was a trend toward decreased startle probability and magnitude in HAD2 rats compared with water-treated controls. CONCLUSIONS: The acoustic startle response to a tone stimulus is a sensitive measure of mild alcohol withdrawal in rats. Rats selectively bred for low alcohol intake showed greater alcohol withdrawal magnitude than did rats selectively bred for high alcohol intake. These results provide further evidence that an inverse genetic association exists between alcohol withdrawal magnitude and propensity toward alcohol drinking in rats.

Alcohol Drinking↗
PubMed2004

Acoustic startle reactivity during acute alcohol withdrawal in rats that differ in genetic predisposition toward alcohol drinking: effect of stimulus characteristics.

BACKGROUND: We have previously reported an association between greater alcohol withdrawal magnitude after a single alcohol exposure and a genetic predisposition toward low alcohol drinking in rats selectively bred for differences in alcohol intake when acoustic startle reactivity to a tone stimulus was used to index acute alcohol withdrawal. The purpose of this study was to examine whether the quality of the acoustic startle stimulus (noise versus tone) is important for detecting a genetic relationship between alcohol withdrawal magnitude and alcohol drinking behavior. METHODS: Alcohol-naive male rats selectively bred for high alcohol intake [alcohol-preferring (P), high-alcohol-drinking (HAD)1, and HAD2] or low alcohol intake [alcohol-nonpreferring (NP), low-alcohol-drinking (LAD)1, and LAD2] received a single intragastric infusion of water or alcohol (4.0 g/20.3 ml/kg; 25% v/v), and acoustic startle test sessions were given at 14, 16, 18, 20, and 24 hr after infusion. Each test session consisted of a 5-min acclimation period followed by random presentation of various white noise stimuli (90, 100, 110, and 120 dB.) RESULTS: Line differences in acoustic startle magnitude under control conditions were present in all three pairs of selectively bred lines; P rats showed a greater startle magnitude relative to NP rats, whereas both LAD lines showed a greater startle magnitude relative to both HAD lines. During alcohol withdrawal, the P, HAD1, and HAD2 lines showed enhanced startle magnitude compared with their water-treated controls. No change in startle magnitude during alcohol withdrawal was found in the NP, LAD1, or LAD2 lines. CONCLUSIONS: In contrast to our prior findings, these results showed a genetic association between high alcohol drinking and a greater startle response magnitude to a noise stimulus during alcohol withdrawal. It seems that the genetic association between alcohol drinking and alcohol withdrawal, as assessed by the acoustic startle response, depends on the quality of the acoustic startle stimulus.

Acoustic Stimulation↗
PubMed2001

Nursing experiences with an alcohol-intoxicated rat dam counteract appetitive conditioned responses toward alcohol.

BACKGROUND: Infant rats detect small amounts of alcohol (175 mg%) that are present in maternal milk whenever the dam is moderately intoxicated with alcohol. Interaction with an alcohol-intoxicated mother during the first 2 weeks of life facilitates the preweanling's subsequent discrimination of alcohol's orosensory attributes and produces conditioned aversion to alcohol. The present study further analyzed the hedonic content of infantile alcohol memories established in the nursing context by testing the interaction between experiences with an alcohol-intoxicated dam and learning procedures aimed at establishing an appetitive conditioned response toward alcohol. METHODS: Experiment 1 was to determine appropriate parameters to establish a reliable conditioned preference for alcohol in 16-day-old infants. For conditioning, intraorally infused sucrose solution (appetitive reinforcer) was paired with alcohol's orosensory cues derived from an acute state of alcohol intoxication (3 g/kg). Two control groups included an unpaired condition and a group given sucrose after water intubation. Infants then were evaluated in an alcohol intake test. Relative to control animals, a reliable conditioned preference for alcohol was registered in paired pups. In experiment 2, these conditioning procedures were applied to infant rats which, before conditioning, suckled from dams subjected to a 2.5 g/kg alcohol dose (intragastric) or from water-treated females during postpartum days 3, 5, 7, 9, 11, and 13. RESULTS: Experiment 2 showed that maternal treatment significantly affected the establishment of conditioned preferences for alcohol. Whereas pups reared by control dams exhibited reliable appetitive conditioning to alcohol, infants raised by alcohol dams completely failed to develop appetitive conditioning. CONCLUSIONS: The present results suggest that alcohol-related memories generated via infantile interactions with an intoxicated dam counteract subsequent conditioning of alcohol ingestion. In conjunction with prior studies, it is concluded that alcohol-related nursing experiences are capable of promoting alcohol memories with a negative hedonic content.

Alcoholic Intoxication↗