The D3 dopamine receptor and substance dependence.

Behavioral sensitization, the progressive and enduring enhancement of certain stimulant-induced behaviors following repetitive drug use, is mediated in part by dopaminergic pathways known to play a role in drug dependence. It has been theorized that sensitization underlies the development of drug craving and initiates addictive behaviors of drug dependence. We propose that down-regulation of D3 dopamine receptor function contributes to sensitization. Rodent locomotion is regulated by the opposing influence of dopamine receptor subtypes, with D3 stimulation inhibiting and concurrent D1/D2 receptor activation stimulating locomotion. The D3 receptor has greater occupancy than D1 or D2 receptors following stimulant drug administration. Sensitization may therefore result in part from greater accommodation of the inhibitory D3 receptor "brake" on locomotion, leading to progressive locomotion increase following repeated stimulant exposure. Further study is needed to test this proposed model, and to clarify the role of individual dopamine receptor subtypes in sensitization and drug dependence.

Craving for alcohol and drugs in animals and humans: biology and behavior.

Research studies indicate that sites and pathways for appetitive drive states, that are located in the limbic system, appear to be responsible for normal and pathological craving for alcohol and other addicting drugs. Pathological craving for alcohol and drugs in humans has been substantiated by animal studies, which have identified neurosubstrates and neurotransmitters associated with behavioral models of addiction. Repetitive administration of alcohol and drugs appears to affect hedonic homeostasis of the appetitive drives leading to the hedonic alleostasis where negative reinforcement exceeds positive returns despite continued drug use. Neuroimaging studies have concentrated on areas in the brain related to reward or reinforcement of alcohol/drug use, but the technique can be employed to find support for a neurosubstrate to distinguish normal craving or "liking" from pathological craving or "wanting" a drug. Identifying the neurobasis of "wanting" a drug long after not "liking it" is central to understanding pathological craving and loss of control over drug use in addiction in humans. Neuroimaging is currently the only method to directly visualize sites for craving in the brain in humans. Neuroimaging techniques will provide methods, which are not possible in animals, for studying addictive disease in humans.

Overview of psychiatric comorbidity. Practical and theoretic considerations.

Psychiatric comorbidity is a common clinical challenge for addiction therapists. The clinician is challenged by the assessment as well as the ongoing management of such cases. Stabilization is complicated by the comorbid problems. Careful use of psychiatric medications can be helpful and collaboration with other health care professionals is usually an important aspect of treatment with this population. There is much evidence that treatment of addiction is cost-effective and some evidence that treatment of dual conditions is also cost-effective.

Treatment outcome of an outpatient treatment program for dually-diagnosed veterans: the Cincinnati Veterans Affairs Medical Center.

The Dual Diagnosis Clinic at the Cincinnati VA Medical Center is an integrated treatment program for veterans who have an Axis I psychiatric illness in addition to a substance dependence problem. With a high staff-to-patient ratio and an individualized approach, the DDC treats many dual diagnosis patients effectively. To demonstrate the effectiveness of this approach, an outcome study was conducted looking at the psychiatric emergency room visits, hospitalization rates, and the average length of stay for 557 DDC patients. Patients were divided into two groups: those who completed the assessment period, and those who did not. Equal periods of time before and after this assessment period were studied. Those who completed were more likely to have had fewer psychiatric emergency room visits (p < 0.000001) after the assessment period than before when compared to dropouts. The engaged group had the same or more hospital admissions after the assessment period than before, while the dropout group had fewer. This suggests that there is a significant disorder of engagement for the dual diagnosis populations, and that the first impact of successful treatment is engagement.

Management of a parturient with an uncorrected atrioventricular canal defect.

A 24-year-old woman at 37 weeks gestation, with an uncorrected atrioventricular canal defect and incipient congestive heart failure is presented. This rare defect is part of the larger group of endocardial cushion defects. The peripartum anesthetic management of this condition has not been described. Our patient had a large atrial septal defect, a common regurgitant atrioventricular valve, a large left-to-right shunt and a small ventricular septal defect. Her pregnancy was maintained until she developed symptoms of congestive heart failure. We discuss her peripartum management, monitoring and anesthetic choices.

Cerebrospinal fluid neuroendocrinology of alcohol misusers.

Cerebrospinal fluid (CSF) neurohumors reflect central nervous system physiology in a way that peripheral indices can not. We reviewed clinical studies of CSF biogenic amines and neurohormones in alcohol misusers during various stages of withdrawal or abstinence and found them difficult to compare because of highly variable experimental methods, reliance on single time collections (lumbar punctures) that fail to control for potential stress-induced effects of the procedure, lack of control for tobacco use, and a paucity of non-alcoholmisusing controls. However, taken together, the data thus far show that a variety of neuroactive substances are reduced in concentration in the CSF of some alcohol misusers. Low CSF levels of corticotropinreleasing hormone, beta-endorphin, norepinephrine, diazepam-binding inhibitor, 5-hydroxyindoleacetic acid and somatostatin have all been reported. Whether the decreased CSF levels of these neurohormones and neurotransmitters are a cause or consequence of alcoholism has not been determined. In fact, further studies using serial or continuous CSF sampling techniques with homogeneous, better-characterized patients and normal volunteers are still needed to establish the precise CSF neurochemical abnormalities in alcohol misusers.

Towards a broader view of recovery.

It is estimated that tobacco use accounts for 25% of the total economic cost of illness in America. Chemically dependent patients have a smoking rate that ranges from 80% to 95% in different studies, almost triple the national average. Despite these staggering statistics, only a handful of chemical dependency treatment programs treat nicotine as an addictive drug and actively encourage their patients to quit. Denial by treatment staff and fears in the Recovery community that Recovery would be jeopardized by quitting are two factors contributing to the reluctance to develop smoke-free programs and treat nicotine dependence. The fear that patients would refuse admission to a facility that prohibits smoking and resistance from staff who smoke appear to be the major barriers to adopting a smoke-free policy. The time has come to face the burdensome costs of tobacco use and to address nicotine dependence in chemical dependents. It is time to develop a broader view of Recovery.

An integrated psychology for the addictions: beyond the Self-Medication Hypothesis.

The Self-Medication Hypothesis (SMH) is a popular explanation for chemical dependencies. The SMH ignores or leaves out important biological research which has explored the mechanisms of reward, motivation to use alcohol/drugs, as well as the impact on mood of chronic, excessive alcohol/drug use. A new psychology is needed which includes this biological research as well as the psychological observations contained in the SMH. Self Psychology is used to create an integrated psychology for the addictions.

Development of smoke-free chemical dependency units.

Until recently, the country's chemical dependency units (CDUs) have not addressed nicotine dependence in a meaningful way for their patients. Most CDUs have accepted exemptions to the smoke-free hospital requirements enacted around the country. Twenty-nine CDU's have been identified which have developed progressive smoke-free policies and begun to treat nicotine dependence in the substance abuser. These CDUs cite three factors--concern for the smoker's health, concern for the health effects of involuntary smoking, and the strong opinion of a key leader--as motivations to implement these policies. Because of the significant resistance to these policies, the strong opinion of a key leader was considered one of the most important factors. Once the policy was in place, these CDUs were surprised that the programs ran so smoothly, including normal census counts. The CDUs used a variety of interventions to help smokers quit. There is considerable need to develop effective interventions suitable for CDUs in the treatment of nicotine dependence.

A rating scale for alcoholic denial.

Denial of alcoholism is a serious obstacle to the successful treatment of an alcoholic. If clinicians can conceptualize and focus on this denial, they may be able to make more effective interventions with alcoholics. Denial in alcoholism, as in other illnesses such as cancer and heart disease, may encompass denial of the entire illness or only denial of some aspect, such as the loss of control over alcohol consumption. The Denial Rating Scale (DRS) has been developed to aid in the identification of denial of alcoholism, as well as to help specify which aspect of alcoholism is being denied. The present report describes the DRS and presents early reliability and validity data in support of its use. Preliminary interrater reliability is adequate, and construct and predictive validity appear promising. Several case studies were included to demonstrate the use of the scale.