Psychometric validation of measures of alcohol expectancies, retrospective subjective response, and positive drinking consequences for use with adolescents.

The Anticipated Effects of Alcohol Scale (AEAS), the Subjective Effects of Alcohol Scale, and the Positive Drinking Consequences Questionnaire (PDCQ) are psychometrically sound measures of alcohol expectancies (expectancies), subjective response to alcohol, and positive drinking consequences, respectively, for use with adults. Prior research using these measures suggests that expectancies, subjective response, and positive drinking consequences are related yet distinct determinants of drinking. The current study presents psychometric evaluations of these measures for use with adolescents including confirmatory factor analyses (CFA) of the previously identified latent structures, internal consistency, and test-criterion relationships. Legally, alcohol cannot be administered to adolescents, so we assessed retrospective subjective response (during the first drinking episode ever [SEAS First] and the most recent drinking episode [SEAS Recent]). The sample comprised 248 Connecticut high school students (53.6% male; mean age 16.50 [1.19] years; 71.4% White) who completed an anonymous survey. CFA confirmed the latent factor structures for each measure. The AEAS, SEAS First, SEAS Recent and the PDCQ were internally consistent (mean α AEAS=0.83; SEAS First=0.88; SEAS Recent=0.89, PDCQ=0.87). AEAS subscales evidenced moderate overlap with corresponding SEAS First subscales (mean=0.36) and SEAS Recent subscales (mean=0.46) and modest overlap with the PDCQ (mean=0.17). Expectancies, subjective response, and positive drinking consequences also accounted for significant variance in monthly drinking, lifetime maximum number of drinks consumed, and alcohol-related problems. In sum, the AEAS, the retrospective SEAS, and the PDCQ are psychometrically sound measures for use with adolescents.

Naloxone challenge in smokers. Preliminary evidence of an opioid component in nicotine dependence.

BACKGROUND: This study used an opioid antagonist challenge procedure to evaluate the responsivity of the endogenous opioid system in nicotine-dependent individuals, as evidenced by naloxone-induced alterations in both behavioral (withdrawal, craving) and neuroendocrine (cortisol levels) parameters. METHODS: Twenty subjects (9 smokers and 11 nonsmokers) participated in 4 laboratory sessions during which they were challenged with 0, 0.8, 1.6, or 3.2 mg/70 kg of naloxone and then monitored for 1 hour for subjective signs and symptoms of opiate-like withdrawal, nicotine craving, and alterations in cortisol levels. RESULTS: Nicotine-dependent subjects evidenced naloxone dose-dependent increases in withdrawal signs and symptoms. Lower doses of naloxone also produced increases in urges to smoke (craving) and tiredness in smokers. Smokers, when compared with nonsmokers, had lower prenaloxone baseline levels of cortisol and attenuated cortisol release in response to challenge with naloxone. CONCLUSIONS: These results provide preliminary evidence to suggest that long-term exposure to cigarette smoke is associated with alterations in the responsivity of the endogenous opioid system and the hypothalamic-pituitary-adrenal axis that may contribute to the development of nicotine dependence.

The delta opioid receptor antagonist naltrindole attenuates both alcohol and saccharin intake in rats selectively bred for alcohol preference.

This study demonstrates that the selective delta receptor antagonists ICI 174864 and naltrindole (NTI) attenuate alcohol intake in a dose-dependent manner, without altering water intake, in rats selectively bred for alcohol preference. ICI 174864 had a very limited duration of action, as evidenced by the fact that suppression of alcohol intake lasted for only an hour following ICI 174864 administration. NTI, when administered in a dose of 10 mg/kg, suppressed alcohol intake by 28%. Increasing the dose of NTI to 15 mg/kg produced a 44% suppression of alcohol intake, but a further increase to 20 mg/kg did not produce greater suppression than was seen with a dose of 15 mg/kg (46% versus 44%, respectively). This suggests that NTI is maximally effective in suppressing alcohol intake at a dose of 15.0 mg/kg. NTI displayed a long duration of action, as evidenced by attenuation of alcohol drinking that lasted for at least 8 h following drug treatment. Administering the maximally effective dose of NTI (15 mg/kg) in two parts, separated by 4 h, served to prolong the duration of action of NTI and produced an attenuation of alcohol intake, but not water intake, that lasted for at least 28 h. The effect of NTI on alcohol intake was not specific for alcohol, as evidenced by the fact that NTI reduced the intake of saccharin solutions with and without alcohol.

The delta 2-opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference.

The relative importance of different opioid receptor types in mediating alcohol drinking behavior compared with the intake of other ingesta can be determined by characterizing the effects of selective opioid antagonists on the intake of various ingesta. Nonselective opioid receptor antagonists suppress the intake of many ingesta including alcohol, food, water, and sweets. Two distinct subtypes of delta-opioid receptors, delta 1 and delta 2, have recently been identified in rodent brain. We have previously reported that naltrindole (NTI), which blocks both delta 1 and delta 2 receptors, suppresses both alcohol and saccharin intake in rats selectively bred for high alcohol preference (P line). We now report that naltriben (NTB), an opioid antagonist that is selective for delta 2-opioid receptors, suppresses alcohol intake in rats of the P line and the effect appears to be both specific for alcohol and independent of alcohol palatability. NTB may reduce alcohol intake by attenuating the reinforcing pharmacological properties of alcohol.

Effect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking.

Beta-funaltrexamine (beta-FNA), a selective mu opioid receptor antagonist, when administered in doses of 10.0, 15.0, and 20.0 mg/kg b.wt., decreased alcohol but not water intake in a dose-dependent manner in rats selectively bred for high alcohol intake (HAD line). Beta-FNA also suppressed the intake of a saccharin solution containing alcohol without altering the intake of a similar solution without alcohol. The results suggest that beta-FNA may prove useful as a pharmacotherapeutic agent for the treatment of alcohol dependence. In a second study, pituitary beta-endorphin gene expression (proopiomelanocortin or POMC messenger ribonucleic acid-mRNA) was compared in another pair of rat lines selectively bred for high or low alcohol intake (alcohol-preferring or P and alcohol-nonpreferring or NP lines). A repeated alcohol challenge (1.0 g/kg b.wt./day, IP for 4 days) produced a greater increase in POMC mRNA in the anterior and neurointermediate lobes of the pituitary of P rats compared with NP rats. The results suggest that a genetic predisposition toward high alcohol drinking may be associated with increased responsiveness of the opioid system to alcohol.

Naturalistic follow-up of drinking behavior following participation in an alcohol administration study.

Administration of alcohol to alcohol-dependent individuals for research purposes, while contributing significantly to the fund of knowledge on etiology and treatment of alcohol dependence, has often raised clinical and ethical concerns that such exposure may adversely affect the individual's motivation to reduce drinking or abstain from drinking. In an attempt to evaluate these concerns, we conducted a naturalistic follow-up of subsequent drinking among individuals who participated in an alcohol self-administration study and also received a brief motivational intervention. Twenty-one non-treatment-seeking alcoholics participated in a study examining the effects of naltrexone on alcohol self-administration. Assessment of drinking during the 3 months following the laboratory study indicated that participants had significantly reduced the total number of drinking days and the number of drinks consumed per occasion, as compared to baseline levels. The findings suggest that participation in alcohol administration research does not adversely influence the subsequent drinking of alcohol-dependent individuals. Further, when the alcohol administration research is conducted carefully, with specific attention to the clinical needs of the participants, the risks of adverse effects on participants' drinking behavior is minimal, and, in fact, there is scientific benefit to society and clinical benefit to the participants with regard to their alcoholism.

Naltrexone-induced nausea in patients treated for alcohol dependence: clinical predictors and evidence for opioid-mediated effects.

Naltrexone, an opiate antagonist, is well tolerated by most alcoholic patients; however, a subset reports significant nausea that can limit the effectiveness of this therapy. The goal of this study was to identify risk factors for naltrexone-precipitated nausea to assist in the development of management strategies to maximize the overall effectiveness of naltrexone. On the basis of the hypothesis that alterations in the endogenous opioid system occur with repeated stimulation of endogenous opioids by alcohol, the authors predicted that the recency and intensity of alcohol use would be related to the risk of naltrexone-induced nausea. One hundred twenty alcohol-dependent subjects participated in an open-label trial of naltrexone. After 5 to 30 days of abstinence, subjects received an initial naltrexone dose of 25 mg followed by a dose of 50 mg daily thereafter for 10 weeks. New-onset adverse effects were rated mild, moderate, or severe after 1 week of naltrexone. Logistic regression analyses were used to predict moderate to severe nausea during the first week of therapy from pretreatment patient characteristics. Moderate to severe nausea was reported by 18 subjects (15%) and was linked to poorer medication compliance and heavier drinking during treatment. Risk of nausea was significantly predicted by age, gender, intensity of drinking, duration of abstinence, and the interaction of abstinence duration and intensity of drinking. At shorter durations of abstinence, lighter drinkers were more likely to experience nausea than heavier drinkers. However, the risk of nausea declined with longer periods of abstinence, particularly for lighter drinkers. Younger age and female gender were associated with higher rates of nausea. These results support the hypothesis that recency and intensity of alcohol use are related to opiate antagonist-precipitated nausea and suggest that long-term alcohol use may result in alterations in the endogenous opioid system. Potential strategies to minimize the risk of nausea in vulnerable individuals are discussed.

Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers.

Nicotine and other constituents of tobacco smoke elevate dopamine (DA) and serotonin (5-HT) levels in brain and may cause homeostatic adaptations in DA and 5-HT transporters. Since sex steroids alter DA and 5-HT transporter expression, the effects of smoking on DA and 5-HT transporter availability may differ between sexes. In the present study, DA and 5-HT transporter availabilities were quantitated using single photon emission computed tomography (SPECT) imaging approximately 22 h after bolus administration of [123I]beta-CIT, an analog of cocaine which labels DA and 5-HT transporters. Forty-two subjects including 21 pairs of age-, race-, and gender-matched healthy smokers and nonsmokers (12 female and 9 male pairs) were imaged. Regional uptake was assessed by the outcome measures, V3", which is the ratio of specific (i.e., ROI-cerebellar activity) to nondisplaceable (cerebellar) activity, and V3, the ratio of specific to free plasma parent. Overall, striatal and diencephalic [123I]beta-CIT uptake was not altered by smoking, whereas brainstem [123I]beta-CIT uptake was modestly higher (10%) in smokers vs. nonsmokers. When subgrouped by sex, regardless of smoking status, [123I]beta-CIT uptake was higher in the striatum (10%), diencephalon (15%), and brainstem (15%) in females vs. males. The sex*smoking interaction was not significant in the striatum, diencephalon, or brainstem, despite the observation of 20% higher brainstem [123I]beta-CIT uptake in male smokers vs. nonsmokers and less than a 5% difference between female smokers and nonsmokers. The results demonstrate higher DA and 5-HT transporter availability in females vs. males and no overall effect of smoking with the exception of a modest elevation in brainstem 5-HT transporters in male smokers. Although these findings are preliminary and need validation with a more selective 5-HT transporter radiotracer, the results suggest that brainstem 5-HT transporters may be regulated by smoking in a sex-specific manner.