Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence

BACKGROUND: The role of the dopamine D2 receptor (DRD2) gene in the development of alcohol abuse or dependence is controversial. The controversy is due in part to the disparate definitions pertaining to the control groups used and to the definitions of subtypes in alcohol dependence. In the Han Chinese population, the alcohol dehydrogenase 1B*2/*2 (ADH1B*2/*2) genotype and the aldehyde dehydrogenase 2*2 (ALDH2*2) allele have been considered as protective factors against alcohol abuse or dependence. Moreover, the ADH1B and ALDH2 genes might be involved in dopamine metabolism. We hypothesized that the ADH1B and ALDH2 genes might interact with the DRD2 gene and that the association between the DRD2 gene and alcohol dependence might be affected by different ADH1B and ALDH2 genotypes. This study examined whether the DRD2 gene is associated with specific subtypes of alcohol dependence and evaluated the relationship between the DRD2 gene and alcohol-metabolizing genes in a specific subtype of alcohol dependence. METHODS: Of the 465 Han Chinese subjects who were recruited for the study, 71 were classified with pure alcohol dependence, 113 with both alcohol dependence and anxiety-depression (ANX/DEP ALC), and 129 with anxiety-depression but without alcohol dependence (ANX/DEP). The remaining 152 subjects were supernormal controls. All subjects were interviewed with the Chinese version of the modified Schedule of Affective Disorders and Schizophrenia-Lifetime; all alcohol dependence, anxiety, and major depressive diagnoses were made according to DSM-IV criteria. RESULTS: The DRD2 gene was not found to be associated with pure alcohol dependence or ANX/DEP, but was found to be associated with ANX/DEP ALC. Furthermore, the association between the DRD2 gene and ANX/DEP ALC was shown to be under the control of the ALDH2*1/*1 and ADH1B*1/*2 genotypes. CONCLUSIONS: ANX/DEP ALC is a specific subtype of alcohol dependence. Because ANX/DEP ALC was associated with the DRD2 gene only under the stratification of ADH1B*1/*2 or ALDH2*1/*1, the DRD2 gene might interact with the ADH1B gene and the ALDH2 gene, respectively, in the development of ANX/DEP ALC in the Taiwan Han Chinese population.     

Aftercare attendance and post-treatment functioning of severely substance dependent residential treatment clients

The present study evaluated the impact of a structured aftercare programme following residential treatment for severe alcohol and/or heroin dependent clients. Over 17 months, 77 participants were recruited to the study and allocated randomly to either a structured aftercare (SA) programme or to unstructured aftercare (UA) of crisis counselling on request. Independent clinicians interviewed participants and collaterals, at 4-month (median) intervals, for 12 months following residential treatment. SA compared to UA was associated with a fourfold increase in aftercare attendance and one-third the rate of uncontrolled principal substance use at follow-up. Participants who attended either type of aftercare relapsed a median of 134 days later than those who attended no aftercare. Overall, 23% of monitored participants remained abstinent throughout, 21% maintained controlled substance use and 56% relapsed, within a median of 36 days following residential treatment. The only significant predictor of days to relapse, controlling for age, was pretreatment use of additional substances. Participants with pretreatment additional substance use relapsed a median of 192 days earlier than those who had used no other substances. The degree of agreement between participant self-reports and collateral reports was fair-to-moderate and moderate among collaterals. Intention-to-treat analyses revealed significant and clinically meaningful reductions in substance use in this sample of severely dependent residential treatment clients. The generalizability of these results is limited because of significant differences in age and presenting substance between the study sample and other clients admitted to the service during the study. This latter group of younger, male, heroin-dependent clients with polydrug use who refuse opioid pharmacotherapy, are more likely to drop out of treatment or relapse early following treatment and continue to present a challenge to treatment services. [Sannibale C, Van den Bossche E, O'Connor D, Zador D, Capus C, Gregory K, McKenzie M. Aftercare attendance and post-treatment functioning of severely substance dependent residential treatment clients. Drug Alcohol Rev 2003;22:181 - 190]     

Stimulus conditioned to foot-shock stress reinstates alcohol-seeking behavior in an animal model of relapse

Rationale. Stress and conditioned responses to drug cues have been implicated as critical factors in relapse to drug use. In the animal literature, both the conditioned effects of drug-related stimuli and the unconditioned effects of foot-shock stress have been well documented to reinstate extinguished drug-seeking behavior. What has remained largely unexplored, however, is the significance of stimuli conditioned to foot-shock stress for the resumption of drug seeking. Additionally, although relapse is often the result of several risk factors acting in combination, the possibility that interactions among risk factors such as conditioned stress and drug cues may intensify drug-seeking behavior has received little experimental attention. Objectives. The purpose of this study was to examine the individual and interactive effects of a stimulus conditioned to foot-shock stress (STRESS CS) and a stimulus conditioned to ethanol reward (EtOH CS) on the reinstatement of ethanol-seeking behavior following extinction. Methods. Male Wistar rats were trained to orally self-administer 10% ethanol on a fixed-ratio 3 schedule of reinforcement. The EtOH CS was established by response-contingently pairing 0.5 s illumination of a white cue light with each reinforced response. The STRESS CS was established by pairing a continuous white noise (70 dB) with intermittent foot shock (10 min; 0.5 mA; 0.5 s on; mean off period of 40 s). Ethanol dependence was induced by an ethanol vapor-inhalation procedure. After ethanol-maintained instrumental responding was extinguished by withholding ethanol and the EtOH CS, reinstatement tests were conducted. Results. Both exposure to the STRESS CS and response-contingent presentation of the EtOH CS reinstated extinguished responding at the previously active, ethanol-paired lever without further ethanol availability. When response-contingent availability of the EtOH CS was preceded by exposure to the STRESS CS, interactive effects of these stimuli on responding were observed. However, both the individual and interactive effects of the STRESS CS and the EtOH CS reached statistical significance only in rats with a history of ethanol dependence but not in ethanol-nondependent rats. Conclusions. The results confirm that both conditioned stress and ethanol cues elicit ethanol-seeking behavior and, more importantly, that these stimuli produce interactive effects resulting in an increased ethanol-seeking response. The findings also indicate that susceptibility to ethanol seeking induced by conditioned stress and alcohol cues depends significantly on the history of prior alcohol exposure.     

Nicotine self-administration and withdrawal: modulation of anxiety in the social interaction test in rats

RATIONALE: Most smokers report smoking has an anxiolytic effect, which may contribute to nicotine dependence. OBJECTIVE: To examine effects in the social interaction test (SI) of anxiety after 4 weeks' self-administered nicotine (15 infusions of 0.03 mg/kg, totalling 0.45 mg/kg per day), and after 24 and 72 h of withdrawal. The effect of exposure to the operant chamber on withdrawal responses was also examined. METHODS: Animals were trained to self-administer saline or nicotine and after 4 weeks they were tested in SI after their daily self-administration session. Animals were retested after 24 and 72 h withdrawal, when they were either taken directly from the home cage or were tested 5 min after a 30-min exposure to the operant chamber. RESULTS: Compared with the saline control group, the animals that had been self-administering nicotine for 4 weeks showed decreased social interaction with no decrease in locomotor activity, indicating a significant anxiogenic effect of the nicotine infusions. There was no change in social interaction after 24 and 72 h withdrawal from chronic nicotine, regardless of whether or not the rats were exposed to the operant chamber just prior to being tested. CONCLUSIONS: Nicotine self-administration is not maintained because of its anxiolytic effect, but despite, or because of, its anxiogenic effect. There was no evidence of an anxiogenic response after either 24 or 72 h of withdrawal and thus increased anxiety on withdrawal from nicotine does not seem to contribute to nicotine self-administration.     

Lack of evidence for opioid tolerance or dependence in rhesus monkeys following high-dose anabolic-androgenic steroid administration

Prolonged use of high-dose anabolic–androgenic steroids (AAS) may induce a dependence syndrome, and emerging evidence suggests that AAS effects on endogenous opioid systems may contribute to AAS abuse. The present study tested the hypothesis that high dose AAS treatment enhances endogenous opioid activity in rhesus monkeys as revealed by 1) tolerance to the antinociceptive effects of the mu opioid agonist morphine and 2) physical dependence as indicated by evidence of opioid withdrawal following administration of the opioid antagonist naloxone. Three rhesus monkeys were treated for 14 days with 3.2 mg/kg/day testosterone propionate, and the effects of morphine (0.32–10 mg/kg) and naloxone (0.01–0.32 mg/kg) were examined both before and during treatment. Morphine antinociception was evaluated using a warm-water tail-withdrawal procedure, and naloxone-precipitated withdrawal was evaluated using checked behavioral signs and measures of ventilatory rate. Chronic testosterone administration for 14 days produced a 100-fold increase in mean plasma testosterone levels. However, testosterone treatment did not significantly alter the antinociceptive effects of morphine, and naloxone did not precipitate signs of opioid withdrawal either before or during testosterone treatment. These data do not support the hypothesis that high-dose AAS treatment enhances endogenous opioid activity in rhesus monkeys in a way that produces opioid tolerance or dependence.     

Before-discharge intervention method in the treatment of alcohol dependence

BACKGROUND: Alcoholics have the fundamental problem of denying dependence on alcohol and minimizing their alcohol-related problems. Therapeutic interventions often fail to help alcoholics become aware of their drinking problem and remain in long-range treatment programs, which is a prerequisite for recovery from alcohol dependence. Methods: Inpatients were assigned to either group 1 or 2 depending on which day of the week they were admitted to the hospital. A newly developed structured intervention method (Before-Discharge Intervention Method, or BDIM) was employed with select (nonrandomized) hospitalized alcoholics in group 1 and their family members before the patients were discharged from the hospital. None of the patients in group 2 received the BDIM. With this intervention method, the alcoholic's family members delivered to him or her verbal messages that conveyed concern about the alcoholic's problem drinking, their observations of the alcoholic's past episodes of drinking problems, and wishes and support for abstinence. Unless patients died during hospitalization or would not be able to attend the hospital follow-up clinic and local self-help groups (Danshukai) after discharge, outcome evaluations were carried out on all patients in groups 1 and 2 during two calendar months, 3 months after the last BDIM patient left the hospital. Outcome measures included patient's and family members' attendance at hospital outpatient follow-up sessions and self-help group meetings, and patient's abstinence. RESULTS: Family members' attendance at hospital follow-up sessions and/or self-help group meetings was significantly higher in group 1 than in group 2. Among the three subgroups of discharged patients in either group 1 or 2-that is, those who lived with their spouse, those who lived with someone other than their spouse, and those who lived alone-only those in group 1 who lived with their spouse did significantly better than their counterparts in group 2 in three treatment outcome measures. However, patients' maintenance of abstinence was significantly better only when they and their family members both attended hospital outpatient follow-up sessions and/or self-help group meetings. We noted no other statistically significant difference between groups 1 and 2 in any of the other two subgroups of discharged or patients in any of the three treatment outcome variables. Irrespective of the BDIM, patients who lived alone did significantly more poorly than either those who lived with their spouse or those who lived with someone other than their spouse in terms of attendance at hospital follow-up sessions and local self-help group meetings and abstinence. CONCLUSIONS: This intervention method can help the alcoholic face the reality of his or her drinking problems and alcohol dependence and thus remain longer in long-range rehabilitation programs, which is a prerequisite for successful recovery from alcohol dependence.     

A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler

Rationale: Nicotine replacement therapy (NRT) in varying forms is becoming widely used. Clinicians, therapists and regulatory authorities are interested in the abuse liability and dependence potential of the different forms. Objectives: To compare the abuse liability and dependence potential of nicotine gum, transdermal patch, spray and inhaler. Methods: 504 male and female smokers seeking help with stopping smoking were randomly allocated to the four products. Measures were taken at the designated quit date, then 1 week, 4 weeks, 12 weeks and 15 weeks later. Smokers were advised to use the product for up to 12 weeks. Those still using the product at the 12-week visit were advised to cease use by week 14. Measures included: pleasantness and satisfaction ratings at weeks 1 and 4 (used as a marker of abuse liability); ratings of feeling dependent on NRT at weeks 1, 4, 12 and 15 (used as a marker of subjective dependence); mood and physical symptoms ratings at weeks 12 and 15 (the change being used to assess physical dependence on NRT), continued usage of NRT at week 15 (used as an marker of behavioural dependence). Results: Average ratings of pleasantness were low. The nicotine patch was rated as less unpleasant to use than all other products. There were no significant differences between the products in terms of satisfaction or subjective dependence except at week 15 when no patch users rated themselves as dependent. Continued use of NRT at week 15 was related to rate of delivery of nicotine from the products – 2% for patch, 7% for gum and inhaler, 10% for spray (P<0.05 for linear association). Among those abstinent for 15 weeks, the figures were: 8%, 25% and 37%, respectively. Stopping NRT use between weeks 12 and 15 was not accompanied by withdrawal discomfort or increased frequency of urges to smoke although subjects stopping inhaler use experienced a mild increase in strength of urges to smoke. We conclude that abuse liability from all four NRT products was low. Subjective dependence was moderate and did not differ across products. Behavioural dependence was modest and was positively related to rate of nicotine delivery. Physicians can reassure their patients that most are able to come off NRT as recommended without discomfort. Received: 9 February 1999 / Final version: 4 January 2000     

Childhood adversity in alcohol- and drug-dependent women presenting to out-patient treatment

Eighty alcohol- and/or drug-dependent women who were consecutive admissions to a representative out-patient alcohol and drug service in Christchurch were interviewed with the aim of establishing the extent of exposure to childhood adversity including childhood sexual, physical and emotional abuse and parental problems. The results show that a sizeable percentage of the women came from backgrounds characterized by parental conflict and alcohol and drug problems. Within their first 15 years 51% were subjected to sexual abuse involving attempted or completed oral, anal or vaginal intercourse and 39% were exposed regularly to physical abuse perpetrated by their parents or main parental figures. Over half reported experiencing emotional abuse rated as being 'very distressing' and two-thirds had been exposed to 'very distressing' parental problems. The main implication for clinical practice arising from the results of this study is the need for the development of a broader approach to alcohol and drug service provision. In order to achieve positive treatment outcomes, alcohol and drug services may need to routinely screen and plan treatment for childhood adversity and associated problems in all clients presenting for alcohol and drug treatment.     

Double-blind evaluation of the effect of acute amantadine on cocaine craving

Single doses of amantadine hydrochloride and placebo were administered in a double-blind cross-over design on separate days to ten actively craving cocaine abusers in treatment. Pharmacological treatment did influence cocaine craving, but amantadine was less effective than placebo.     

海洛因依赖者戒毒前后肝肾功能的变化

目的:探讨海洛因依赖者在戒毒前后肝、肾功能的变化.方法:收集武汉市戒毒中心60例住院患者戒毒前后的丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血尿素氮(BUN)、血肌酐(Cr)及尿液α1 MG、清蛋白(ALB)的检测结果,将之与湖北省新华医院70例健康体检者的肝、肾功能检测结果相比较.结果:海洛因依赖者戒毒前血清ALT、AST、尿液α1 MG、ALB含量均显著高于对照组,而血清BUN、Cr则变化不明显;戒毒后,血清ALT、AST较戒毒前有所降低,但仍明显高于对照组,尿液α1 MG、ALB则趋于正常.结论:海洛因依赖者存在肝肾功能损害,其中肾功能损害较轻,宜用早期诊断指标如尿液α1 MG、ALB监测;肝功能损害有一定的持续性,不能完全随戒毒治疗而恢复.提示在进行戒毒治疗的同时,要密切监测肝、肾功能,并了解其变化规律,以利综合治疗.