Searched for: person:rotroj01 or bogenm02 or hanseh03 or lewisc12 or Sarah Mennenga or rosss01 or kc16
A food restriction protocol that increases drug reward decreases tropomyosin receptor kinase B in the ventral tegmental area, with no effect on brain-derived neurotrophic factor or tropomyosin receptor kinase B protein levels in dopaminergic forebrain regions
Pan, Y; Chau, L; Liu, S; Avshalumov, M V; Rice, M E; Carr, K D
Food restriction (FR) decreases brain-derived neurotrophic factor (BDNF) expression in hypothalamic and hindbrain regions that regulate feeding and metabolic efficiency, while increasing expression in hippocampal and neocortical regions. Drugs of abuse alter BDNF expression within the mesocorticolimbic dopamine (DA) pathway, and modifications of BDNF expression within this pathway alter drug-directed behavior. Although FR produces a variety of striatal neuroadaptations and potentiates the rewarding effects of abused drugs, the effects of FR on BDNF expression and function within the DA pathway are unknown. The primary purpose of the present study was to examine the effect of FR on protein levels of BDNF and its tropomyosin receptor kinase B (TrkB) receptor in component structures of the mesocorticolimbic pathway. Three to four weeks of FR, with stabilization of rats at 80% of initial body weight, did not alter BDNF or TrkB levels in nucleus accumbens, caudate-putamen, or medial prefrontal cortex. However, FR decreased TrkB levels in the ventral tegmental area (VTA), without change in levels of BDNF protein or mRNA. The finding that FR also decreased TrkB levels in substantia nigra, with elevation of BDNF protein, suggests that decreased TrkB in VTA could be a residual effect of increased BDNF during an earlier phase of FR. Voltage-clamp recordings in VTA DA neurons indicated decreased glutamate receptor transmission. These data might predict lower average firing rates in FR relative to ad libitum fed subjects, which would be consistent with previous evidence of decreased striatal DA transmission and upregulation of postsynaptic DA receptor signaling. However, FR subjects also displayed elevated VTA levels of phospho-ERK1/2, which is an established mediator of synaptic plasticity. Because VTA neurons are heterogeneous with regard to neurochemistry, function, and target projections, the relationship(s) between the three changes observed in VTA, and their involvement in the augmented striatal and behavioral responsiveness of FR subjects to drugs of abuse, remains speculative
PMCID:3210415
PMID: 21945647
ISSN: 1873-7544
CID: 141070
The association between parental risk behaviors during childhood and having high risk networks in adulthood
Rudolph, Abby E; Jones, Kandice C; Latkin, Carl; Crawford, Natalie D; Fuller, Crystal M
BACKGROUND: Prior research suggests that both social networks and parent drug use influence individual drug use among adolescents and that peers continue to influence drug use among adults. This analysis aims to determine whether parent drug use during childhood is associated with having drug-using networks in adulthood after adjusting for individual adult drug use. METHODS: 650 young adult drug users were recruited through targeted street outreach and respondent-driven sampling in New York City (2006-2009). Baseline surveys ascertained demographics, network characteristics, drug use behaviors, and parental drug use during childhood. Negative binomial regression was used to evaluate this association. RESULTS: The median age was 33 years, 22% injected, 49% were Black, and during childhood 26% of mothers, 32% of fathers, and 13% of primary caregivers used drugs. After adjustment, having >1 parent who used drugs was associated with having a greater proportion of drug using (Adjusted Prevalence Ratio [APR]=1.18; 95%CI: 1.01-1.38) and specifically crack-smoking networks (APR=1.71; 95%CI: 1.21-2.43) in adulthood. Females' networks consisted of more drug users (APR=1.18; 95%CI: 1.01-1.38), injectors (APR=1.44; 95%CI: 1.09-1.90), crack smokers (APR=1.48; 95%CI: 1.18-1.87) and heroin users (APR=1.43; 95%CI: 1.13-1.81); blacks had a greater proportion of crack smoking (APR=1.41; 95%CI: 1.09-1.82), but a smaller proportion of injecting (APR=0.64; 95%CI: 0.43-0.94) and heroin smoking (APR=0.60; 95%CI: 0.47-0.77) networks as adults. CONCLUSIONS: These data suggest that parental drug use is independently associated with having drug-using networks in adulthood. Interventions that target parents and caregivers and that promote drug cessation could impede risky network formation in both adolescents and adults.
PMCID:3178717
PMID: 21632187
ISSN: 1879-0046
CID: 1535652
American Indian methamphetamine and other drug use in the Southwestern United States
Forcehimes, Alyssa A; Venner, Kamilla L; Bogenschutz, Michael P; Foley, Kevin; Davis, Meredith P; Houck, Jon M; Willie, Ericke L; Begaye, Peter
To investigate the extent of methamphetamine and other drug use among American Indians (AIs) in the Four Corners region, we developed collaborations with Southwestern tribal entities and treatment programs in and around New Mexico. We held nine focus groups, mostly with Southwestern AI participants (N = 81) from three diverse New Mexico communities to understand community members, treatment providers, and clients/relatives views on methamphetamine. We conducted a telephone survey of staff (N = 100) from agencies across New Mexico to assess perceptions of methamphetamine use among people working with AI populations. We collected and analyzed self-reported drug use data from 300 AI clients/relatives who completed the Addiction Severity Index (ASI) in the context of treatment at three diverse addiction treatment programs. Each focus group offered a unique perspective about the effect of drugs and alcohol on each respective community. Though data from the phone surveys and ASIs suggested concerning rates of methamphetamine use, with women more adversely affected by substance use in general, alcohol was identified as the biggest substance use problem for AI populations in the Southwest. There appears to be agreement that methamphetamine use is a significant problem in these communities, but that alcohol is much more prevalent and problematic. There was less agreement about what should be done to prevent and treat methamphetamine use. Future research should attend to regional and tribal differences due to variability in drug use patterns, and should focus on identifying and improving dissemination of effective substance use interventions.
PMCID:3415471
PMID: 21988577
ISSN: 1099-9809
CID: 1478102
Individual, study, and neighborhood level characteristics associated with peer recruitment of young illicit drug users in New York City: optimizing respondent driven sampling
Rudolph, Abby E; Crawford, Natalie D; Latkin, Carl; White, Kellee; Benjamin, Ebele O; Jones, Kandice; Fuller, Crystal M
Recruiting a representative sample using respondent driven sampling (RDS) relies on successful peer recruitment. While prior studies have identified individual-level characteristics associated with peer recruitment, study- and neighborhood-level factors may also influence peer recruitment. This analysis aimed to identify individual-, study-, and neighborhood-level factors associated with RDS peer recruitment. 390 young adult (18-40 years) heroin, crack and/or cocaine users in New York City (NYC) were recruited via RDS into a cohort study aiming to identify social risk factors for transitioning from non-injection to injection drug use (2006-2009). Individual-level baseline characteristics (demographics, drug use, and network characteristics) and study factors (number of recruitment coupons received and participant attendance at RDS training sessions (RDST) on peer recruitment) were ascertained. Aggregate measures of neighborhood attitudes about drug use, drug users, and HIV were obtained from a separate anonymous NYC resident random-digit-dialing survey (2002) and linked with baseline data by zip code. Descriptive statistics and multilevel modeling were used to identify factors associated with peer recruitment. After adjustment, recruiting each additional eligible peer recruit was associated with receiving additional recruitment coupons, RDST attendance, and a greater proportion of community residents in one's recruitment neighborhood believing that clean needles should be made available to IDUs; heroin use was negatively associated with recruiting additional eligible peers. After adjustment, recruiting each additional peer (regardless of eligibility) was associated with receiving additional recruitment coupons and RDST attendance. Our data highlight the importance of neighborhood factors and suggest that RDS may not be as effective in areas characterized by negative attitudes about drug use. Group-facilitated recruitment training sessions may help counter negative social norms when implementing RDS in drug user studies.
PMCID:3171638
PMID: 21852029
ISSN: 1873-5347
CID: 1535662
Effects of food restriction and sucrose intake on synaptic delivery of AMPA receptors in nucleus accumbens
Peng XX; Ziff EB; Carr KD
Insertion and removal of AMPA receptors from the synaptic membrane underlie dynamic tuning of synaptic transmission and enduring changes in synaptic strength. Preclinical addiction research suggests that AMPA receptor trafficking plays an important role in nucleus accumbens (NAc) neuroplasticity underlying the compulsive and persistent quality of drug-seeking. Considering the parallels between drug addiction and compulsive eating, plus the supranormal reward properties of sucrose, and the role of dieting as a risk factor in development of binge pathology, the present study used a biochemical subcellular fractionation approach to determine whether brief intake of a 10% sucrose solution increases synaptic delivery of AMPA receptors in NAc of chronically food-restricted (FR) relative to ad libitum fed (AL) rats. FR, alone, produced a small but significant increase in synaptic expression of AMPA receptors. This may contribute to NAc integrative mechanisms that mediate the enhanced behavioral responsiveness of FR subjects to phasic reward stimuli, including food and drugs. Brief intake of sucrose increased GluR1 in the PSD, regardless of dietary condition, though the net effect was greater in FR than AL subjects. A marked increase in GluR2 was also observed, but only in FR rats. This set of results suggests that in FR subjects, sucrose may have primarily increased delivery of GluR1/GluR2 heteromers to the PSD, while in AL subjects sucrose increased delivery of GluR2-lacking channels. The functional consequences of these possible differences in subunit composition of trafficked AMPA receptors between diet groups remain to be determined. Nevertheless, the present set of results suggest a promising new avenue to pursue in the effort to understand synaptic plasticity involved in adaptive and pathological food-directed behavior and the mechanistic basis of severe dieting as a risk factor for the latter. Synapse, 2011. (c) 2011 Wiley-Liss, Inc
PMCID:3146970
PMID: 21425350
ISSN: 1098-2396
CID: 134092
SKF-83566, a D(1) -dopamine receptor antagonist, inhibits the dopamine transporter
Stouffer, Melissa A; Ali, Solav; Reith, Maarten E A; Patel, Jyoti C; Sarti, Federica; Carr, Kenneth D; Rice, Margaret E
J. Neurochem. (2011) 118, 714-720. ABSTRACT: Dopamine (DA) is an important transmitter in both motor and limbic pathways. We sought to investigate the role of D(1) -receptor activation in axonal DA release regulation in dorsal striatum using a D(1) -receptor antagonist, SKF-83566. Evoked DA release was monitored in rat striatal slices using fast-scan cyclic voltammetry. SKF-83566 caused a concentration-dependent increase in peak single-pulse evoked extracellular DA concentration, with a maximum increase of approximately 65% in 5 muM SKF-83566. This was accompanied by a concentration-dependent increase in extracellular DA concentration clearance time. Both effects were occluded by nomifensine (1 muM), a dopamine transporter (DAT) inhibitor, suggesting that SKF-83566 acted via the DAT. We tested this by examining [(3) H]DA uptake into LLc-PK cells expressing rat DAT, and confirmed that SKF-83566 is a competitive DAT inhibitor with an IC(50) of 5.7 muM. Binding studies with [(3) H]CFT, a cocaine analog, showed even more potent action of SKF-83566 at the DAT cocaine binding site (IC(50) = 0.51 muM). Thus, data obtained using SKF-83566 as a D(1) DA-receptor antagonist may be confounded by concurrent DAT inhibition. More positively, however, SKF-83566 might be a candidate to attenuate cocaine effects in vivo because of the greater potency of this drug at the cocaine versus DA binding site of the DAT
PMCID:3337772
PMID: 21689106
ISSN: 1471-4159
CID: 136635
Design of NIDA CTN Protocol 0047: screening, motivational assessment, referral, and treatment in emergency departments (SMART-ED)
Bogenschutz, Michael P; Donovan, Dennis M; Adinoff, Bryon; Crandall, Cameron; Forcehimes, Alyssa A; Lindblad, Robert; Mandler, Raul N; Oden, Neal L; Perl, Harold I; Walker, Robrina
BACKGROUND: Medical settings such as emergency departments (EDs) present an opportunity to identify and provide services for individuals with substance use problems who might otherwise never receive any form of assessment, referral, or intervention. Although screening, brief intervention, and referral to treatment models have been extensively studied and are considered effective for individuals with alcohol problems presenting in EDs and other medical settings, the efficacy of such interventions has not been established for drug users presenting in EDs. OBJECTIVES: This article describes the design of a NIDA Clinical Trials Network protocol testing the efficacy of an screening, brief intervention, and referral to treatment model in medical EDs, highlighting considerations that are pertinent to the design of other studies targeting substance use behaviors in medical treatment settings. METHODS: The protocol is described, and critical design decisions are discussed. RESULTS: Design challenges included defining treatment conditions, study population, and site characteristics; developing the screening process; choosing the primary outcome; balancing brevity and comprehensiveness of assessment; and selecting the strategy for statistical analysis. CONCLUSION: Many of the issues arising in the design of this study will be relevant to future studies of interventions for addictions in medical settings. SCIENTIFIC SIGNIFICANCE: Optimal trial design is critical to determining how best to integrate substance abuse interventions into medical care.
PMCID:3168577
PMID: 21854285
ISSN: 0095-2990
CID: 1478122
Smoking Cessation Treatment among Patients in Community-Based Substance Abuse Rehabilitation Programs: Exploring Predictors of Outcome as Clues Toward Treatment Improvement
Reid, Malcolm S; Jiang, Huiping; Fallon, Bryan; Sonne, Susan; Rinaldi, Paul; Turrigiano, Eva; Arfken, Cynthia; Robinson, James; Rotrosen, John; Nunes, Edward V
Background: Predictors of smoking cessation (SC) treatment outcome were explored in a multisite clinical trial of SC treatment at community-based, outpatient, substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment Clinical Trials Network. Objectives: To explore baseline demographic and clinical predictors of abstinence during treatment. Methods: Cigarette smokers from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned to SC treatment as an adjunct to substance abuse treatment as usual or to substance abuse treatment as usual. SC treatment consisted of group counseling (weeks 1-8) plus transdermal nicotine patch treatment (21 mg/day, weeks 1-6; 14 mg/day, weeks 7-8). Demographic and clinical predictors of smoking abstinence were evaluated among those patients assigned to the active SC condition (N = 153) using logistic regression. Results: Abstinence during treatment was positively associated with younger age, Hispanic or Caucasian (as opposed to African American) ethnicity/race, employment or student status, fewer cigarettes per day at baseline, lower severity of the primary substance problem at baseline, and higher methadone doses (among the subsample in methadone treatment). Conclusions and Scientific Significance: During future efforts to improve SC treatments among drug- and alcohol-dependent patients, consideration should be given to adequate treatment to reduce the severity of the primary drug or alcohol problem, tailoring treatments for patients with greater severity of smoking and of the primary substance problem, and culturally sensitive interventions. Analysis of predictors of outcome may be a useful tool for treatment development
PMCID:4101995
PMID: 21854292
ISSN: 1097-9891
CID: 136946
Food scarcity, neuroadaptations, and the pathogenic potential of dieting in an unnatural ecology: Binge eating and drug abuse
Carr, Kenneth D
In the laboratory, food restriction has been shown to induce neuroadaptations in brain reward circuitry which are likely to be among those that facilitate survival during periods of food scarcity in the wild. However, the upregulation of mechanisms that promote foraging and reward-related learning may pose a hazard when food restriction is self-imposed in an ecology of abundant appetitive rewards. For example, episodes of loss of control during weight-loss dieting, use of drugs with addictive potential as diet aids, and alternating fasting with alcohol consumption in order to avoid weight gain, may induce synaptic plasticity that increases the risk of enduring maladaptive reward-directed behavior. In the present mini-review, representative basic research findings are outlined which indicate that food restriction alters the function of mesoaccumbens dopamine neurons, potentiates cellular and behavioral responses to D-1 and D-2 dopamine receptor stimulation, and increases stimulus-induced synaptic insertion of AMPA receptors in nucleus accumbens. Possible mechanistic underpinnings of increased drug reward magnitude, drug-seeking, and binge intake of sucrose in food-restricted animal subjects are discussed and possible implications for human weight-loss dieting are considered
PMCID:3107914
PMID: 21530562
ISSN: 1873-507x
CID: 134091
Enhanced cocaine-conditioned place preference and associated brain regional levels of BDNF, p-ERK1/2 and p-Ser845-GluA1 in food-restricted rats
Liu S; Zheng D; Peng XX; Cabeza de Vaca S; Carr KD
Previously, a learning-free measure was used to demonstrate that chronic food restriction (FR) increases the reward magnitude of a wide range of abused drugs. Moreover, a variety of striatal neuroadaptations were detected in FR subjects, some of which are known to be involved in synaptic plasticity but have been ruled out as modulators of acute drug reward magnitude. Little is known about effects of FR on drug-conditioned place preference (CPP) and brain regional mechanisms that may enhance CPP in FR subjects. The purpose of the present study was to compare the expression and persistence of a conditioned place preference (CPP) induced by a relatively low dose of cocaine (7.0mg/kg, i.p.) in ad libitum fed (AL) and FR rats and take several brain regional biochemical measures following the first CPP conditioning session to probe candidate mechanisms that may underlie the more robust CPP observed in FR subjects. Behaviorally, AL subjects displayed a CPP upon initial testing which extinguished rapidly over the course of subsequent test sessions while CPP in FR subjects persisted. Despite previous reports of elevated BDNF protein in forebrain regions of FR rats, the FR protocol used in the present study did not alter BDNF levels in dorsal hippocampus, nucleus accumbens or medial prefrontal cortex. On the other hand, FR rats, whether injected with cocaine or vehicle, displayed elevated p-ERK1/2 and p-Ser845-GluA1 in dorsal hippocampus. FR rats also displayed elevated p-ERK1/2 in medial prefrontal cortex and elevated p-ERK1 in nucleus accumbens, with further increases produced by cocaine. The one effect observed exclusively in cocaine-treated FR rats was increased p-Ser845-GluA1 in nucleus accumbens. These findings suggest a number of avenues for continuing investigation with potential translational significance
PMCID:3119777
PMID: 21640333
ISSN: 1872-6240
CID: 134090