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Biomedical subjects

D B Newlin

Publications and source records attributed to D B Newlin.

At least 19 recordsLinked to original sources

Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers.

Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.

Alcoholism

A comparison of drug conditioning and craving for alcohol and cocaine.

Craving is a potentially important concept that is difficult to define and study in the laboratory. Although alcohol and cocaine are very different pharmacologically, this discussion emphasizes common factors in addiction to these drugs, such as the tendency of alcoholics and cocaine abusers to crave these substances. I review commonalities in drug conditioning and cue reactivity to alcohol and cocaine. Both drugs support Pavlovian conditioning when they are presented as unconditioned stimuli, whether studied in rodents or humans. In addition, both drugs are craved when abusers are presented with stimuli associated with these drugs. Finally, I propose a theoretical definition of craving based on autoshaping and sign-tracking phenomena that suggests a common mechanism of addiction to these drugs. This model defines craving as a reflection of sign tracking to internal and external stimuli that have in the past reliably predicted presentation of these drugs.

Alcoholism

Cardiovascular responses to naloxone challenge in opiate-dependent individuals.

Vagally mediated tachycardia appears to be a common response to abused drugs and, therefore, has implications for abuse liability. To test the specificity of this common factor, we determined whether the tachycardia to naloxone in opiate-dependent individuals has a significant vagal component. Naloxone challenge (0.4 mg, IM) in 19 opiate-dependent men and women was associated with highly reliable tachycardia, but no significant change in vagal tone index, a noninvasive measure of parasympathetic inhibitory control of the heart. We conclude that tachycardia during naloxone-precipitated withdrawal is not vagally mediated. Thus, there is some degree of specificity to the common factor of vagally mediated tachycardia to abused drugs because it was ruled out in at least one drug (naloxone) with aversive subjective effects.

Adult

Nonassociative mechanisms in preferences for alcoholic flavors: differences between sons of alcoholics and sons of nonalcoholics.

We studied nonassociative processes in the development of preferences for wine flavors in high- and low-risk groups for alcoholism. Twenty college-age sons of nonalcoholics had greater "Liking" ratings for red wine flavors to which they had 20 prior exposures in the laboratory than flavors to which they had been exposed five times or zero times. Fourteen sons of alcoholics did not show this mere exposure effect. The results indicate differences between high- and low-risk groups for alcoholism in the nonassociative process by which preference for particular alcoholic flavors is established.

Adult

Chronic tolerance and sensitization to alcohol in sons of alcoholics.

In view of conflicting results concerning differences between sons of alcoholics and sons of nonalcoholics in response to a single alcohol challenge (with a given dose), we exposed these high and low risk groups to several sessions in which they drank alcohol at the same dose in order to measure the development of chronic tolerance or sensitization with repeated doses. Sons of alcoholics and sons of nonalcoholics received a moderate dose of alcohol (0.5 g/kg) in three sessions with alcohol, followed by a placebo session. Sons of alcoholics developed reverse tolerance or chronic sensitization to repeated dosings of alcohol in finger pulse amplitude, while sons of nonalcoholics did not. Sons of alcoholics failed to show chronic tolerance in skin conductance and finger temperature, while sons of alcoholics did show the development of tolerance. Sons of alcoholics demonstrated greater motor activity throughout the sessions, both before and after alcohol. These results indicate that high and low risk groups differ in terms of their developmental adaptation to alcohol, as well as in the temperamental trait of behavioral activity.

Alcohol Drinking

Prior exposures to the laboratory enhance the effect of alcohol.

We compared responses to 0.6 g/kg alcohol of normal male drinkers in a laboratory environment that was new to the subjects with the responses of a second group in the same environment who had two prior exposures to the laboratory environment and procedures. Alcohol-induced increases in heart rate, cheek temperature and self-reported intoxication were greater in the subjects who had previous exposure to the laboratory environment than in the subjects who had no such previous exposure. Differences in blood alcohol concentration (BAC) also were found between the two environments. However, differences in the physiological and self-report measures were found after matching subjects in terms of BAC. These results suggest that novelty effects may contaminate alcohol responses in novel laboratory environments, and they add to our understanding of nonpharmacological factors in the responses to drugs.

Adult

Alcohol challenge with sons of alcoholics: a critical review and analysis.

Studies are reviewed in which response to acute administration of alcohol was compared between individuals with and without family histories of alcoholism (FH+, FH-). This research represents a search for a psychobiological marker for alcoholism. A methodological critique of the procedures reported in this literature is then presented. Finally, a conceptual model is suggested in which differences in the response to alcohol between FH+ individuals and FH- individuals must be understood in relation to time after drinking alcohol. This Newtonian differentiator model proposes that sons of alcoholics exhibit acute sensitization as blood alcohol level rises and acute tolerance as blood alcohol level falls, compared with sons of nonalcoholics. Therefore, FH+ subjects find alcohol more rewarding because they accentuate the pleasurable, excitatory aspects of initial intoxication and attenuate the feelings of anxiety and depression that predominate as blood alcohol levels drop.

Acetaldehyde

Vagal mediation of the effect of alcohol on heart rate.

Alcohol (0.5 g/kg bodyweight) was administered in two sessions and placebo in a third session to normal, healthy social drinkers. A control group was administered a mixer (i.e., no alcohol) for each of the three sessions. The heart rate and vagal tone index (V) response patterns were different to alcohol than to the mixer or placebo. The treatments did not differentially influence pulse transit time. The results indicated that the acute effect of a moderate dose of alcohol on the heart is parasympathetically (i.e., vagally) mediated and has no significant direct sympathetic component.

Adult

Sons of alcoholics report greater hangover symptoms than sons of nonalcoholics: a pilot study.

We investigated alcohol-induced hangovers among college men at high and low risk for alcoholism. Thirteen sons of alcoholics reported significantly (p less than 0.001) greater hangover symptoms in the past year than 25 sons of nonalcoholics. The two groups reported comparable quantity-frequency of recent drinking. To the extent that hangover represents an acute withdrawal syndrome to alcohol, this raises the question of whether sons of alcoholics are "dependence-prone."

Adult

Autonomic and subjective responses to alcohol stimuli with appropriate control stimuli.

Previous studies on "craving" for alcohol after exposure to olfactory stimuli for alcohol may be criticized on the grounds that the control stimuli were not really appropriate. We included exposure to a preferred nonalcoholic beverage and to a sweet food item as additional control stimuli in order to better compare the salivary, autonomic, and self-reported craving responses of alcoholics with normal social drinkers. The results indicated that the salivation measure was differentially sensitive to the alcohol stimulus, even when compared to appropriate control stimuli. It is possible that self-reported craving is a biased measure in alcoholic inpatients in treatment.

Adult

The skin-flushing response: autonomic, self-report, and conditioned responses to repeated administrations of alcohol in Asian men.

This study examined the skin-flushing response in Asian men, which is a low-risk factor for alcoholism. Asian men who did and did not flush to alcohol consumed 0.5 g/kg ethanol during three sessions with alcohol, and placebo in a fourth session. The results indicated that: (a) Asian men who flushed to alcohol showed pronounced cardiovascular changes that did not exhibit differential tolerance over 3 sessions, (b) there were surprisingly few self-reported mood differences in response to alcohol between those who did and did not flush, and (c) finger-pulse amplitude decreased and self-ratings of "boastful" increased significantly in response to placebo challenge in those men who did not flush. These results raise questions about the psychological mechanisms by which the skin-flushing response inhibits the development and expression of alcoholism.

Alcoholism

Placebo responding in the same direction as alcohol in women.

Pavlovian conditioning studies with alcohol in humans have been performed exclusively with men subjects. Men demonstrate a placebo response opposite in direction to alcohol, which Newlin (Alcohol Clin Exp Res 9:411-416, 1985) termed an antagonistic placebo response. The current study used normal women subjects given alcohol, placebo, or a soft drink control. Placebo significantly (p less than 0.05) increased heart rate compared to the control condition, and this placebo response was in the same direction as the effect of alcohol. The correlation of heart rate change with reported intoxication was +0.44 in women, when it was negative in men (Newlin DB: Alcohol Clin Exp Res 9:411-416, 1985). These results, when considered in relation to other data concerning individual differences in antagonistic placebo responding, suggest a pattern in which risk for alcoholism is negatively related to placebo responding.

Adult

Effects of alcohol conditioning and expectancy on a visuo-motor integration task.

Two experiments were performed in which the classical conditioning model of tolerance, the habituation theory of tolerance, and state dependent learning theory made conflicting predictions. In the first experiment, alcohol conditioning did not produce a compensatory response under placebo on a visuo-motor integration task, but disguised alcohol produced a large decrement in performance. Since the results were consistent both with habituation and state dependent learning theories, a second experiment was performed in which all subjects received alcohol, but half were told that they were receiving pure tonic water. The finding of no expectancy effect was inconsistent with habituation theory, but fully consistent with state dependent learning theory.

Adult

Alcohol expectancy and conditioning in sons of alcoholics.

This paper presents an overview of research performed in the context of a classical conditioning model of addiction to alcohol. College age sons of alcoholics were administered placebo in a single session or alcohol in repeated sessions in the laboratory. Sons of alcoholics had enhanced autonomic responses to placebo that were opposite in direction to the effect of alcohol, and they showed reverse tolerance to alcohol in three conditioning sessions. These studies are discussed in relation to theories of addiction to alcohol and a speculative model of risk for alcoholism.

Adolescent

Conditioned compensatory response to alcohol placebo in humans.

An autonomic response opposite in direction to the effect of alcohol (i.e., a conditioned compensatory response) was found in normal social drinkers given alcohol placebo. Seven males received placebo in a distinctive drinking room after receiving vodka and tonic in two sessions in the same room; seven more males received distilled water in three sessions in that room. The response to placebo, consisting of decreased pulse transit time and finger skin temperature, was antagonistic to alcohol. The results support the application of the classical conditioning model of alcoholism to humans.

Autonomic Nervous System