Faculty Bibliography

Surveillance data suggests that club drug use (Ecstasy, GHB, ketamine, LSD, methamphetamine, PCP and flunitrazepam) has been a predominantly White adolescent and young adult phenomenon in the United States. The authors investigated the use of club drugs among 323 street-recruited minority substance users in northern New York City (66.3% were Hispanic, 23.8% were Black, and 9.9% were White/other race; median age = 32 years old). While Whites were more likely than others to have used club drugs, club drug use among Hispanics and Blacks was not uncommon; 45.3% Hispanics and 56.4% of Blacks reported a lifetime history of club drug use. PCP was the most commonly reported club drug used among all racial/ethnic groups. Further investigation of club drug use in minority populations is warranted.

RATIONALE: Prior research indicates that psychostimulant-induced sensitization is not expressed in lateral hypothalamic electrical self-stimulation (LHSS)-based measures of drug reward, although the augmenting effect of chronic food restriction is. Neuroadaptations within the brain dopamine system have been identified in both psychostimulant-sensitized and food-restricted animals. Consequently, a variant of the LHSS paradigm in which responding is particularly sensitive to changes in dopaminergic tone may be best suited to detect and compare effects of chronic d-amphetamine and food restriction. Instrumental responding on a progressive ratio (PR) schedule is more sensitive to dopaminergic manipulations than is responding on a continuous reinforcement (CRF) schedule, but has not previously been used to examine chronic psychostimulant and food restriction effects on LHSS-based measures of drug reward. OBJECTIVE: The first aim of this study was to determine whether a regimen of d-amphetamine treatment, that produces locomotor sensitization (5 mg/kg per day x5 days), increases the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The second aim, was to determine whether chronic food restriction produces a marked increase in the reward-potentiating effect of d-amphetamine in the PR LHSS protocol and, if so, whether it is reversible in parallel with body weight recovery when free feeding is restored. METHOD: Reward-potentiating effects of a challenge dose of d-amphetamine (0.25 mg/kg, IP) were measured in terms of the break point of LHSS responding on a PR schedule of reinforcement, in ad libitum fed and food-restricted rats. RESULTS: A regimen of d-amphetamine treatment that produced locomotor sensitization did not increase the break point for LHSS in the presence or absence of d-amphetamine. Chronic food restriction produced a marked increase in the break point-increasing effect of d-amphetamine (3-fold), which returned to baseline in parallel with body weight recovery over a 4-week period of restored free-feeding. CONCLUSIONS: A locomotor-sensitizing regimen of d-amphetamine treatment does not increase the rewarding effect of LH electrical stimulation or the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The augmenting effect of chronic food restriction on drug reward is mechanistically and functionally different from psychostimulant sensitization and may be controlled by signals associated with adipose depletion and repletion

OBJECTIVE: There is limited evidence suggesting a link between posttraumatic stress disorder (PTSD) and Attention-Deficit/ Hyperactivity Disorder (ADHD). This study examined the association between PTSD and ADHD using retrospective and current clinical evaluations. METHOD: Twenty-five male veterans with PTSD and 22 male veterans with panic disorder were evaluated for ADHD. The data was analyzed using chi-square and student's t-tests. RESULTS: Thirty-six percent of participants with PTSD and 9% of participants with panic disorder met criteria for childhood ADHD. Twenty-eight percent of participants with PTSD and 5% of participants with panic disorder met criteria for current ADHD. CONCLUSIONS: There appears to be a significant association of PTSD with ADHD. ADHD or common predisposing factors may increase the vulnerability for developing PTSD

Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating

Hepatitis C virus (HCV) burdens injection drug users (IDUs) with prevalence estimated from 60-100% compared to around 5% among noninjection drug users (non-IDUs). We present preliminary data comparing the risk for HCV among IDUs and non-IDUs to inform new avenues of HCV prevention and intervention planning. Two cohorts, new IDUs (injecting < or =3 years) and non-IDUs (smoke/sniff heroine, crack or cocaine < or =10 years), ages 15-40, were street-recruited in New York City. Participants underwent risk surveys and HCV serology at baseline and 6-month follow-up visits. Person-time analysis was used to estimate annual HCV incidence. Of 683 non-IDUs, 653 were HCV seronegative, 422 returned for at least 1 follow-up visit, and 1 became HCV seropositive. Non-IDUs contributed 246.3 person-years (PY) yielding an annual incident rate of 0.4/100 PY (95% Confidence Interval [CI]=0.0-1.2). Of 260 IDUs, 114 were HCV seronegative, 62 returned for at least 1 follow-up visit, and 13 became HCV seropositive. IDUs contributed 36.3 PY yielding an annual incidence rate of 35.9/100 PY (95%CI=19.1-61.2). Among IDUs, HCV seroconverters tended to be younger (median age 25 vs. 28, respectively), and inject more frequently (61.5% vs. 34.7%, respectively) than non-seroconverters. These interim data suggest that IDUs may have engaged in high-risk practices prior to being identified for prevention services. Preventing or at least delaying transition into injection could increase opportunity to intervene. Identifying risk factors for transition into injection could inform early prevention to reduce onset of injection and risk of HCV.

Current approaches to prevention of blood-borne infections in injection drug users include referral to drug abuse treatment, access to sterile syringes, bleach disinfection of injection equipment, and education about not sharing equipment. However, rates of some blood-borne infections (e.g., hepatitis C virus) remain elevated among injection drug users, especially early after initiation into injection drug use. With lower infection rates in noninjectors and transition into injection drug use occurring most commonly among these noninjectors, prevention of transition into injection drug use as an additional step to reduce risk for acquisition and transmission of blood-borne infections merits closer attention.

The Expanded Syringe Access Demonstration Program (ESAP), which was intended to increase access to syringes for injection drug users (IDUs), went into effect in New York State on 1 January 2001. ESAP allowed prescription-authorized health care providers to register to distribute syringes without a prescription. In spring 2002, we conducted a random postal survey of 1100 providers in New York City to evaluate involvement in ESAP and willingness to furnish IDUs with syringes. Among 363 nurse practitioners, physicians, and physician assistants responding, 16.9% knew about ESAP, and 2.0% believed they were registered; 50.5% would consider distributing syringes to patients who were IDUs. Most of those unwilling to distribute syringes were concerned about legal and moral issues. More respondents agreed that providers should prescribe syringes than distribute syringes (41.1% vs. 22.7%; P<.0001). These results suggest that many providers are willing to furnish IDUs with syringes but are unaware of the current law.

BACKGROUND: Atypical antipsychotics are increasingly used in clinical practice in the management of borderline personality disorder (BPD), and a small but growing body of literature supports their efficacy. Here, we report the results of a double-blind, placebo-controlled study of olanzapine as a treatment for BPD. METHOD: Forty BPD patients (25 female, 15 male) were randomly assigned in equal numbers to olanzapine and placebo. Diagnoses were made using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders and the Mini-International Neuropsychiatric Interview. Patients with schizophrenia, bipolar disorder, or current major depression were excluded. Olanzapine dosage was flexible, and the dose range was 2.5 to 20 mg/day, with most patients receiving 5 to 10 mg/day. No concomitant psychotropic medications were allowed. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks. The primary outcome was change in the total score for the 9 BPD criteria on a 1-to-7 Likert scale, the Clinical Global Impressions scale modified for borderline personality disorder (CGI-BPD), using an analysis of covariance model including baseline score as covariate. Data were collected from July 2000 to April 2002. RESULTS: Olanzapine was found to be significantly (p <.05) superior to placebo on the CGI-BPD at endpoint, with separation occurring as early as 4 weeks. Similar results were found for the single-item Clinical Global Impressions scale. Weight gain was significantly (p =.027) greater in the olanzapine group. CONCLUSIONS: This study supports the efficacy of olanzapine for symptoms of BPD in a mixed sample of women and men. Further studies with olanzapine and other atypical antipsychotics are needed.

Results of behavioral and c-fos immunohistochemical studies have suggested that chronic food restriction and maintenance of animals at 75-80% of free-feeding body weight may increase d-1 dopamine (DA) receptor function. The purpose of the present study was to determine whether D-1 DA receptor binding and/or mitogen-activated protein kinase (MAPK) signaling in caudate-putamen (CPu) and nucleus accumbens (NAc) are increased in food-restricted subjects. In the first experiment, saturation binding of the D-1 DA receptor antagonist [3H]SCH-23390 indicated no difference between food-restricted and ad libitum fed rats with regard to density or affinity of d-1 binding sites in CPu or NAc. In the second experiment, activation of extracellular signal-regulated kinases (ERK1/2) and cyclic AMP response element-binding protein (CREB) by i.c.v. injection of the D-1 DA receptor agonist SKF-82958 (20 microg) were markedly greater in food-restricted than ad libitum fed rats. Given a prior finding that SKF-82958 does not differentially stimulate adenylyl cyclase in CPu or NAc of food-restricted versus ad libitum fed subjects, the present results suggest that increased D-1 DA receptor-mediated ERK1/2 MAP kinase signaling may mediate the enhanced downstream activation of CREB, c-fos, and behavioral responses in food-restricted subjects. It is of interest that food restriction also increased the activation of c-Jun N-terminal protein kinase/stress-activated protein kinase, but this effect was no greater in rats injected with SKF-82958 than in those injected with saline vehicle. This represents additional evidence of increased striatal cell signaling in food-restricted subjects, presumably in response to the i.c.v. injection procedure, although the underlying receptor mechanisms remain to be determined. There were no differences between feeding groups in protein levels of the major phosphatases, MKP-2 and PP1. The upregulation of striatal MAP kinase signaling in food-restricted animals may adaptively serve to facilitate associative learning but, at the same time, increase vulnerability to the rewarding and addictive properties of abused drugs