Faculty Bibliography

OBJECTIVE: Existing research indicates that increased self-efficacy to sustain abstinence is a strong causal mechanism explaining later reduction of drinking. Little is known about how mechanisms of change may differ among distinct subgroups of alcoholics. The purpose of this study was to evaluate the mediational role of self-efficacy on changes in drinking associated with Alcoholics Anonymous (AA) attendance in Type-A and Type-B alcoholics. METHOD: Analysis of covariance and structural equation modeling were used to model 6-, 9-, 12-, and 15-month data from Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) participants who were classified as Type-A or Type-B alcoholics (N=1,284; 72% male). Measures of AA attendance and percent days abstinent were taken from the Form 90. Self- efficacy was assessed with the Alcohol Abstinence Self-Efficacy Scale. RESULTS: Alcoholism typology and AA attendance were independent predictors of later self-efficacy, but there was no interaction between typology and AA attendance. Abstinence self-efficacy mediated a modest proportion of the effect of posttreatment AA attendance on later abstinence in both Type-A and Type-B alcoholics. The strength of this mediation did not differ by typology. CONCLUSIONS: Self-efficacy for abstinence has a strong direct relationship to abstinence across treatment conditions and typologies. Increases in self-efficacy mediate some of the beneficial effects of AA for Type-A and Type-B alcoholics. Further work is necessary to determine whether self-efficacy plays a different role in the recovery of Type-A versus Type-B alcoholics.

Illicit drug users sustain the epidemics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis C (HCV), and sexually transmitted infections (STIs). Substance abuse treatment programs present a major intervention point in stemming these epidemics. As a part of the 'Infections and Substance Abuse' study, established by the National Drug Abuse Treatment Clinical Trials Network, sponsored by National Institute on Drug Abuse, three surveys were developed; for treatment program administrators, for clinicians, and for state and District of Columbia health and substance abuse department administrators, capturing service availability, government mandates, funding, and other key elements related to the three infection groups. Treatment programs varied in corporate structure, source of revenue, patient census, and medical and non-medical staffing; medical services, counseling services, and staff education targeted HIV/AIDS more often than HCV or STIs. The results from this study have the potential to generate hypotheses for further health services research to inform public policy

Twelve Steps (TS) has demonstrated effectiveness; induction into Alcoholics Anonymous (AA) is a primary objective of TS and is a pivotal mechanism explaining its effectiveness. However, evidence suggests that, after treatment, dropout from AA is high. This study investigated whether alcohol problem severity predicted both AA affiliation and disaffiliation among clients receiving TS. This study of a Project MATCH sample included 453 alcohol-dependent clients randomly assigned to TS who reported AA attendance during treatment. Greater alcohol problem severity predicted AA attendance; opposite to prediction, less alcohol-impaired clients were more than twice as likely to discontinue AA attendance after treatment. When sustained AA attendance is desired, the evaluation of client pretreatment alcohol involvement may be useful for identifying potential AA dropout after TS treatment. Findings also indicate that, among treatment-seeking problem drinkers, AA dropout and disaffiliation are distinct, albeit correlated, constructs that require future investigation.

It was previously reported that chronic food restriction and maintenance of rats at 75-80% of initial body weight enhanced the reward-potentiating effect of D-amphetamine in the lateral hypothalamic self-stimulation (LHSS) paradigm. Moreover, the enhancement reversed in parallel with body weight recovery when ad libitum access to food was reinstated. The present study tested the hypothesis that hypoleptinemia during food restriction is necessary for expression of enhanced drug reward. In Experiment 1, intracerebroventricular (i.c.v.) infusion of leptin (0.5 microg/0.5 microl/hr for 8 days) in food-restricted rats did not alter the rewarding effect of D-amphetamine (0.5 mg/kg, i.p.). Considering that i.c.v. leptin may not diffuse into deep brain regions where direct effects on drug reward sensitivity may be exerted, effects of acute bilateral microinjection of leptin (0.5 microg) in ventral tegmental area and nucleus accumbens were tested in Experiment 2 and found to have no effect. In Experiment 3, chronic i.c.v. leptin infusion in ad libitum fed rats decreased food intake and body weight and enhanced the rewarding effect of D-amphetamine. Sensitivity to D-amphetamine returned to normal as body weight recovered following cessation of leptin infusion. This result suggests that weight loss, whether from hormone-induced appetite suppression or experimenter-imposed food restriction, is sufficient to enhance drug reward sensitivity. Experiment 4 tested whether food restriction in the absence of body weight loss alters drug reward sensitivity. Rats received chronic i.c.v. infusion of the orexigenic melanocortin receptor antagonist, SHU9119 (0.02 microg/0.5 microl/hr for 12 days), and a subset were pair-fed to vehicle-infused controls. Although these subjects ingested approximately 50% of the amount of food ingested by free-feeding SHU9119-infused rats, they displayed no weight loss and no change in sensitivity to D-amphetamine. Together, results of this study support the importance of weight loss, but not leptin, in the enhancement of drug reward sensitivity

The present communication reports on DA uptake in rat striatum in a model of chronic food restriction. The K(m) for DA uptake was unaltered, but the V(max) was reduced by 32%, not supporting the idea that the enhanced behavioral sensitivity to cocaine or d-amphetamine upon chronic food restriction is due to a greater density of DAT at the plasma membrane for drug interaction. Chronic food restriction did not alter the potency of cocaine or D-amphetamine in inhibiting DA uptake in the striatum, suggesting that the enhanced behavioral sensitivity to these drugs upon chronic food restriction is not due to their enhanced affinity for DAT. These results point to factors other than DAT density or affinity underlying the sensitized response to psychostimulants in food restriction

In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest.

Chronic food restriction increases exploratory behavior, cognitive function, and the rewarding effects of abused drugs. Recently, striatal neuroadaptations that may be involved in these effects were observed. Specifically, D-1 dopamine (DA) receptor agonist challenge produced stronger activation of extracellular signal-regulated kinase (ERK), calcium-calmodulin-dependent kinase II (CaMKII), and the nuclear transcription factor cAMP response element binding protein (CREB) in nucleus accumbens (NAc) of food-restricted (FR) relative to ad libitum fed (AL) rats. Further, when FR rats were injected intracerebroventricularly (i.c.v.) with vehicle (saline) they displayed stronger activation of c-Jun N-terminal protein kinase (JNK), ERK and CaMKII than did AL rats. It is not known to what extent the latter effects represent the basal state of FR rats or an amplified response to the brief handling involved in the i.c.v. injection procedure. Using Western blotting it was found that basal phospho-JNK is higher in caudate-putamen (CPu) and NAc of FR relative to AL rats. Interestingly, brief handling decreased phospho-JNK levels in FR subjects. Basal phospho-ERK1/2 also tended to be elevated in CPu and NAc of FR rats but the elevation was not significant. However, phospho-MEK--the activated kinase upstream of ERK1/2--was significantly elevated in NAc of FR rats. Neither ERK1/2 nor MEK were activated by brief handling. CaMKII was selectively activated by handling in NAc of FR rats, suggesting a state-dependent response to a salient event. Given the established involvement of mitogen-activated protein kinase (MAPK) and CaMKII in synaptic plasticity, learning and memory, the increase in basal phospho-MEK and hyperresponsiveness of CaMKII in NAc may represent adaptive cellular responses to persistent negative energy balance that facilitate associative learning in connection with food-seeking

The authors reviewed the empirical literature concerning the use of twelve-step programs and treatments by patients with co-occurring substance use disorders and other psychiatric disorders. Strong evidence was found that dually diagnosed individuals (DDI), with the possible exception of those with psychotic disorders, attend twelve-step programs at rates comparable to non-DDI. Twelve-step involvement is consistently associated with improved substance use outcomes. Although there have been numerous clinical trials involving twelve step-oriented interventions for DDI, most of the studies suffered from substantial methodological limitations. More work is needed to determine what kinds of twelve-step treatments and programs are effective for various types of patients and elucidate the mechanisms by which these approaches facilitate recovery.