Faculty Bibliography

The role of 12-step programs and 12-step-oriented treatments for dually diagnosed individuals (DDI) remains unclear. Here are presented the results of a pilot study in which 10 seriously mentally ill patients received a modified 12-step facilitation (TSF) therapy emphasizing engagement of DDI in a specialized 12-step program for DDI. Participants significantly increased their 12-step attendance and decreased their substance use during the 12 weeks of treatment. Larger and longer-term studies are needed to assess the efficacy of modified TSF for DDI relative to other treatments, and to determine what forms of TSF are most effective in this population.

Alcohol use disorders (AUDs) include a spectrum of alcohol-related disorders such as alcohol misuse, abuse, and dependence. AUDs are a group of common, chronic diseases caused by a complicated interaction between biological, psychological, social, and cultural factors. Approximately two-thirds of all American adults, 18 years of age and older, drink some alcohol during the course of a year. Moreover, approximately 7.5% of the United States population (approximately 14 million people) meet criteria for alcohol abuse or dependence. At present, there are two types of medications that are used to treat alcoholism. The first are aversive medications, with disulfiram being the most commonly used. By causing an aversive reaction when taken with alcohol, these medications deter further alcohol consumption through negative reinforcement. However, they are limited in utility unless given in a supervised setting. The second, are those that have anti-craving effects. One of the medications, naltrexone, an opiate antagonist, was first approved by the Food and Drug Administration in 1994. Since there is a limited number of biological interventions for alcoholism at present, most treatment consists of nonpharmacologic psychosocial treatments.

(from the journal abstract) Despite a growing body of literature indicating an increase in alcohol use disorders (AUDs) among the elderly, this group of patients has historically been ignored. The elderly are a vulnerable group who suffer a disproportionate amount of physical and psychosocial distress. Any alcohol use in this population, but especially excessive use, poses unique problems biologically, psychologically, and socially. This article will summarize the classification, prevalence, assessment, and treatment of AUDs in the elderly, with an emphasis on the special needs and unique aspects of engaging and treating this patient population.

Biological drive states exert homeostatic control in part by increasing the reinforcing effects of environmental incentive stimuli. An apparent by-product of this adaptive response is the enhanced acquisition of drug self-administration behavior in food-restricted (FR) animals. While previous research has demonstrated increased central sensitivity to rewarding effects of abused drugs and direct dopamine (DA) receptor agonists in FR subjects, the underlying neurobiology is not well understood. Recently, it was demonstrated that intracerebroventricular (i.c.v.) injection of the D-1 DA receptor agonist, SKF-82958 produces a stronger activation of striatal extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element-binding protein (CREB) in FR relative to ad libitum (AL) fed rats. The main purpose of the present study was to characterize the involvement and mechanisms of interaction between NMDA receptor function and the augmented cellular responses to D-1 DA receptor stimulation in nucleus accumbens (NAc) of FR rats. In experiment 1, Western immunoblotting was used to demonstrate that i.c.v. injection of SKF-82958 (20 microg) produces greater phosphorylation of the NMDA NR1 subunit and calcium-calmodulin kinase II (CaMK II) in NAc of FR as compared with AL rats. In experiment 2, pretreatment of subjects with the NMDA antagonist, MK-801 (1.0 mg/kg, i.p.) decreased SKF-82958-induced activation of CaMK II, ERK1/2 and CREB, and reversed the augmenting effect of FR on activation of all three proteins. In experiment 3, pretreatment with the mitogen-activated protein kinase/ERK kinase inhibitor SL-327 (60 mg/kg, i.p.) suppressed SKF-82958- induced activation of ERK1/2 and reversed the augmenting effect of FR on CREB activation. These results point to specific neuroadaptations in the NAc of FR rats whereby D-1 DA receptor stimulation leads to increased NMDA NR1 subunit phosphorylation and consequent increases in NMDA receptor-dependent CaMK II and ERK1/2 signaling, and increased NMDA receptor/ERK1/2-dependent phosphorylation of the nuclear transcription factor, CREB. The upregulated cellular responses to D-1 DA agonist challenge may play a role in the augmentation of drug reward and appetitive instrumental learning during periods of food restriction

The objective of the study was to explore correlates of suicidal ideation among African Americans in a community-based cohort in Baltimore, Md. Participants had initiated use of heroin, crack, or cocaine by means other than injection in the prior 10 years. An interview-administered questionnaire collected information regarding drug use history, depressive symptoms, drug dependence, and suicidal thoughts and attempts within the past six months. Multiple logistic regression was used to identify factors independently associated with suicidal ideation. Of 148 persons, median age was 27 years, and 60.8% were female. Suicidal ideation was reported by 21.6% of participants. Those reporting suicidal ideation were significantly more likely to be dependent on two or more drugs (adjusted odds ratio=2.93, 95% confidence interval = 1.25, 6.88). Our findings underscore the need to integrate treatment for psychiatric comorbidity and drug dependence and target these services toward young, African-American drug users.

Surveillance data suggests that use of ecstasy in the U.S. is predominantly among white adolescent and young adults. To investigate ecstasy use among substance users in New York City we added questions to ongoing efforts to recruit heroin and cocaine users. Of 715 participants recruited, 58.3% were injection drug users (IDUs). The median age was 32 (range 17-64), 76.4% were male, 49.0% were currently homeless, 62.4% were Hispanic, 27.3% were black, and 34.5% were born outside the United States. Overall, 23.4% used ecstasy in their lifetime and 11.9% had used in the last-6 months. In multivariate logistic regression, correlates of lifetime ecstasy use included younger age, being born in the U.S., and current homelessness. We observed a significant interaction between injection drug use and race where, compared to black non-IDUs, Hispanic non-IDUs, and white IDUs were significantly more likely to have a history of lifetime ecstasy use while black IDUs were significantly less likely. These findings are limited to persons who use other drugs, but suggest that further investigation of ecstasy use in minority populations is warranted.

Recently, attention has turned to the possibility that endocrine adiposity hormones, such as leptin, may regulate appetitively motivated behavior by modulating brain dopamine function. By extension, it has been hypothesized that the increased behavioral sensitivity of food-restricted, underweight rats to psychostimulant challenge may be triggered by the accompanying hypoleptinemia. The purpose of the present study was to determine whether two weeks of continuous intracerebroventricular (ICV) infusion of leptin alters the motor-activating effect of D-amphetamine (0.75 mg/kg, IP) in food-restricted rats. Lateral ventricular infusion of leptin, using a regimen that decreases food intake and body weight in ad libitum fed rats (12 microg/day), had no effect on the locomotor response to D-amphetamine in food-restricted rats that were maintained at 80% of prerestriction body weight. This result may indicate that hypoleptinemia is not involved in the induction/maintenance of neuroadaptations that mediate enhanced behavioral sensitivity to psychostimulant challenge. Interestingly, ad libitum fed rats treated with leptin displayed an increased locomotor response to D-amphetamine that was most prominent 3-5 days after termination of the infusion. Body weights and D-amphetamine sensitivity of these subjects returned to control values by 8-10 days postinfusion. The enhanced behavioral sensitivity to D-amphetamine in leptin-treated ad libitum fed rats may be a by-product of adipose depletion and, if so, would further support involvement of a peripheral signal other than hypoleptinemia in the modulation of central sensitivity to psychostimulant challenge

BACKGROUND: Chronic food restriction augments the rewarding effect of centrally administered psychostimulant drugs and this effect may involve a previously documented upregulation of D-1 dopamine receptor-mediated MAP kinase signaling in nucleus accumbens (NAc) and caudate-putamen (CPu). Psychostimulants are known to induce striatal glutamate release, and group I metabotropic glutamate receptors (mGluR) have been implicated in the cellular and behavioral responses to amphetamine. The purpose of the present study was to evaluate whether chronic food restriction increases striatal MAP kinase signaling in response to the group I mGluR agonist, DHPG. RESULTS: Western immunoblotting was used to demonstrate that intracerebroventricular (i.c.v.) injection of DHPG (500 nmol) produces greater activation of ERK1/2 and CREB in CPu and NAc of food-restricted as compared to ad libitum fed rats. Fos-immunostaining induced by DHPG was also stronger in CPu and NAc core of food-restricted relative to ad libitum fed rats. However, i.c.v. injection of saline-vehicle produced greater activation of ERK1/2 and CREB in CPu and NAc of food-restricted relative to ad libitum fed rats, and this difference was not seen when subjects received no i.c.v. injection prior to sacrifice. In addition, although DHPG activated Akt, there was no difference in Akt activation between feeding groups. To probe whether the augmented ERK1/2 and CREB activation in vehicle-injected food-restricted rats are mediated by one or more GluR types, effects of an NMDA antagonist (MK-801, 100 nmol), AMPA antagonist (DNQX, 10 nmol), and group I mGluR antagonist (AIDA, 100 nmol) were compared to saline-vehicle. Antagonist injections did not diminish activation of ERK1/2 or CREB. CONCLUSIONS: These results indicate that a group I mGluR agonist induces phosphorylation of Akt, ERK1/2 and CREB in both CPu and NAc. However, group I mGluR-mediated signaling may not be upregulated in food-restricted rats. Rather, a physiological response to 'i.c.v. injection stress' is augmented by food restriction and appears to summate with effects of the group I mGluR agonist in activating ERK1/2 and CREB. While the augmented cellular response of food-restricted rats to i.c.v. injection treatment represents additional evidence of enhanced CNS responsiveness in these subjects, the functional significance and underlying mechanism(s) of this effect remain to be elucidated