Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117 e103

increases in dependence among both male and female smokerswho reported consuming 16–25 cigarettes per day. We also foundthis trend among women who smoked 0–15 cigarettes per day.Smoking to reduce irritability/restlessness became a more accuratemarker of severe dependence among men, and smoking to relievecraving became a marker of more severe dependence, and a moreaccurate marker of dependence, among women.

Conclusions: Overall, we found that dependence may be declin-ing among male smokers, likely due to reduced consumption.However, there may have been increases in dependence amongboth male and female “pack-a-day” smokers, and dependence itselfmay have changed to be better identified by withdrawal-relatedsymptoms, suggesting a harder to treat smoking population.

Financial support: NIDA, PA50DA03394502 (PI: McKee); NIMH,T32MH01423539 (PI: Zhang).

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.646

Carvedilol treatment reduces cocaine use inmethadone-maintained cocaine users

Mehmet Sofuoglu 1,2, Theresa Babuscio 2,Kathleen M. Carroll 2,1

1 Psychiatry, VA CT Healthcare System, West Haven,CT, United States2 Psychiatry, Yale University, New Haven, CT, UnitedStates

Aims: The goal of this study was to test the effectivenessof carvedilol (CAR) for reducing cocaine use in a double-blind,placebo-controlled study. CAR, a mixed alpha1- and beta-adrenergic receptor blocker. We hypothesized that CAR will bemore effective than placebo in reducing cocaine use, as measuredby cocaine urine results and self-report cocaine use.

Methods: 106 opioid and cocaine-dependent individuals wererandomized to one of three treatment groups: placebo (n = 34),25 mg/day CAR (n = 37) or 50 mg/day CAR (n = 35). Participantsattended clinic six days per week to complete weekly assessments,submit thrice weekly urine samples, and ingest study medicationunder direct observations. The study had 3 phases: methadoneinduction (2 weeks), treatment (13 weeks) and detoxification (4weeks). Baseline characteristics of participants were comparedusing chi-square tests for categorical variables and ANOVA for con-tinuous measures. Continuous and ordinal outcomes were analyzedwith a Hierarchical Linear Modeling.

Results: The 3 treatment groups were comparable for basicdemographic variables and for the severity of cocaine and otherdrug use. No significant differences were found for treatment reten-tion across the groups: 56% of the placebo, 76% of 25 mg and 66%of 50 mg CAR group (p > 0.05). The proportion (SD) of cocaine posi-tive urines during the trial were lower for the 25 mg CAR, 0.5 (0.4),condition, compared to placebo, 0.9 (0.4), or 50 mg CAR, 0.7 (0.3), [F(2,91) = 3.6, p < 0.05]. The proportion of heroin positive urines, werenot significantly different for the 25 mg CAR, 0.4 (0.4), 50 mg CAR,0.4 (0.3) or placebo 0.5 (0.3) condition [F (2,91) = 0.8, p > 0.05]. Thenumber of days of cocaine abstinence during the past 2 weeks ofthe trial did not show treatment differences: 7.8 (4.9) for placebo,8.1 (5.0) for CAR 25 mg, and 6.4 (4.7) for CAR 50 mg [F (2,82) = 0.9,p > 0.05].

Conclusions: These findings warrant further clinical trials usingCAR with daily doses of 25 mg/day or lower in patients with cocainedependence.

Financial support: Supported by the VA MIRECC and NIDA R01DA019885 grants.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.647

Decreased norepinephrine transporter functionin the orbitofrontal cortex and enhancedcocaine abuse risk following adolescentmethylphenidate treatment in a rat model ofAttention Deficit Hyperactivity Disorder

Sucharita S. Somkuwar 1, Kathleen Kantak 2, LindaP. Dwoskin 1

1 Pharmaceutical Sciences, University of Kentucky,Lexington, KY, United States2 Psychology, Boston University, Boston, MA, UnitedStates

Aims: Methylphenidate (MPH) reduces symptoms of Atten-tion Deficit Hyperactivity Disorder (ADHD) by inhibiting dopamineand norepinephrine transporters (DAT and NET) in the medialprefrontal cortex (mPFC) and orbitofrontal cortex (OFC). In theSpontaneously Hypertensive Rat (SHR) model of ADHD, adoles-cent MPH treatment increased cocaine self-administration, andincreased DAT function in mPFC (not OFC) during adulthood com-pared to VEH control and MPH-treated Wistar–Kyoto (WKY) andWistar (WIS) controls. Herein, we tested the hypothesis that MPHtreatment during adolescence alters NET function in mPFC and OFCof adult SHR.

Methods: SHR, WKY and WIS rats (n = 8–9/gp) received oralMPH (1.5 mg/kg) or VEH (1 ml/kg) daily from P28-55. Between P77-91, NET function was determined using in vivo voltammetry. Afterlocal ejection of NE (100 ffJM, with GBR12909, 50 nM), peak ampli-tude (Amax) and first-order rate constant of uptake (k − 1) of NEwere recorded. NE uptake rate was calculated as Amax × k − 1.

Results: In mPFC, no strain or treatment differences wererevealed for NE uptake rate. In OFC, an interaction was obtainedfor NE uptake rate (F [2,45] = 4.4, p < 0.05). NE uptake rate for VEH-SHR (1.3 nM/s) was 5.2-fold greater than VEH controls and wasdecreased (p < 0.05) by MPH during adolescence to control levels.

Conclusions: Increased OFC NET function in SHR maycontribute to ADHD-like symptoms and the greater cocaineself-administration compared to WKY and WIS. MPH duringadolescence normalized OFC NET function during adulthood,which may contribute to reductions in ADHD-like symptoms. TheMPH-induced normalization of OFC NET function suggests thatthis mechanism does not underlie the enhanced cocaine self-administration in adulthood.

Financial support: DA011716 and KO Fellowship (SSS).

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.648

Oxidative stress, BDNF and severity of crackcocaine use in early withdrawal

Anne O. Sordi, Flavio Pechansky, Felix Kessler,Lisia von Diemen

Psychiatry – Addiction, Center for Drug and AlcoholResearch (CPAD), Hospital de Clínicas de Porto Alegre(HCPA), Universidade Federal do Rio Grande do Sul(UFRGS), Porto Alegre, RS, Brazil, Porto Alegre, Brazil

Aims: An important goal of addiction research is to discover neu-robiological markers that could predict severity of addiction andhelp to determine the appropriate treatment. The aim of this study

e104 Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117

is to evaluate alteration in oxidative stress markers thiobarbituricacid reactive substances (TBARS) and brain-derived neurotrophicfactor (BDNF) among crack cocaine users during early withdrawaland its relationship to severity of drug use.

Methods: Longitudinal study with 49 adults crack cocaine userswith positive urine cocaine test on their first day of hospitalizationat public psychiatric hospital and 49 healthy controls with a neg-ative urine cocaine test from a neighborhood similar to where thecases came from. Blood samples were collected at intake and dis-charge for the analysis of TABRS and BDNF. Detailed informationabout crack cocaine use was assessed by the Addiction SeverityIndex-6th Version (ASI-6). Severity of crack use was estimatedusing information from age of first crack use, years of crack useand crack rocks used in the previous 30 days.

Results: There is a significant negative correlation betweenTBARS and BDNF levels at discharged (r = −0.294, p = 0.043) evenwhen controlled for age and days of hospitalization. TBARS levelsare positively correlated to severity of crack use (r = 0.304, p = 0.04)and BDNF levels are negatively correlated to severity of crack use(r = −0.359, p = 0.014).

Conclusions: TBARS and BDNF blood levels are inversely corre-lated during early crack cocaine withdrawal, and this is related tothe severity of crack use. Therefore TBARS and BDNF could be possi-ble markers of the severity of crack cocaine addiction and cerebralplasticity during early withdrawal.

Financial support: Secretaria Nacional Anti-Drogas – SENADFundo de Incentivo a Pesquisa e Eventos – FIPE.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.649

The role of discrimination, ethnic identity, andacculturation in substance use patterns amongMexican origin transnational youth

Fernando I. Soriano 1, J.C. Anthony 1,3, FelipeCastro 1, Ietza Bojorquez 1,2

1 Human Development, California State UniversitySan Marcos, San Marcos, CA, United States2 Department of Epidemiology, Michigan StateUniversity, East Lansing, MI, United States3 Department of Psychology, University of Texas, ElPaso, TX, United States

Aims: Aims Under the Obama administration, the Department ofHomeland Security has deported an average of 400,000 persons peryear who are undocumented, many of these are young people whospent a significant amount of time in the U.S. and who can be con-sidered “transnational youth”. For this presentation, transnationalyouth are defined as young people between the ages of 15 and 24who have un-willfully moved or were transported to Mexico afterliving in the U.S. for at least 5 years. This presentation will reviewextant findings from studies focusing on this growing populationin Mexico. A theoretical discussion will highlight the importantrole of discrimination, acculturation and ethnic identity in affectingthe health and mental health status, while delineating how thesefactors are tied to varying patterns of drug and alcohol use. A the-oretical model will be presented accounting for such factors anddelineating their role in substance use and abuse.

Methods: This is a theoeretical/commentary abstract.Results: This is a theoeretical/commentary abstract.Conclusions: Findings from the limited number of studies sug-

gest the importance of discrimination, acculturation and ethnic

identity in influencing the use of drugs and alcohol among transna-tional youth. These findings point to the need to address thepsychosocial and cultural needs of transnational youth throughtargeted prevention and intervention programs.

Financial support: Financial Support NIDA training fellowshipawarded to second author.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.650

Serotonin (5-HT)2C receptor interaction withprotein phosphatase and tensin homologueresults in distinct patterns of cortical ERK1/2activation

Claudia Soto 1,2, Noelle C. Anastasio 1,2, RachelHartley 1,2, Robert G. Fox 1,2, Huang Chi Du 3,Scott Gilbertson 3, Kathryn Cunningham 1,2

1 Ctr for Addiction Res, UTMB, Galveston, TX, UnitedStates2 Dept Pharm&Tox, UTMB, Galveston, TX, UnitedStates3 Dept Chem, Univ Houston, Houston, TX, UnitedStates

Aims: Relapse vulnerability in cocaine dependence is propelledby impulsivity and linked to damped serotonin 2C receptor (5-HT2CR) tone in the medial prefrontal cortex (mPFC). Normalizationof 5-HT2CR signaling may be possible by targeting protein:proteininteractions with 5-HT2CR as a therapeutic target.

Protein phosphatase and tensin homologue (PTEN) is a pro-tein partner of the 5-HT2CR which controls receptor activationstates. Interestingly, disruption of the 5-HT2CR:PTEN complex bypeptide TAT-3L4F potentiates 5-HT2CR signaling and normalizesimpulsivity, albeit through an unknown mechanism. The 5-HT2CRis G-protein coupled-receptor through which activation resultsin extracellular regulated kinases 1&2 (ERK1/2) phosphorylation(pERK1/2). Here, we test the hypothesis that agonist stimulation of5-HT2CR and/or pharmacological disruption of the 5-HT2CR:PTENcomplex will result in distinct patterns of pERK1/2 in rodent mPFC.

Methods: Outbred, male Sprague-Dawley rats were adminis-tered (i.p.) saline (1 ml/kg), 5-HT2CR agonist WAY163909 (1 mg/kg),TAT-3L4F (10 ffJmol/kg), or the combination of WAY163909 plusTAT-3L4F. Rats were sacrificed 20 min post-treatment and mPFCtissue wascollected; nuclear and soluble protein fractions wereobtained by differential centrifugation and pERK1/2 levels evaluatedby immunoblotting.

Results: WAY163909 alone produced an increase in cytoso-lic and nuclear pERK1/2 levels in the mPFC as compared to saline(p < 0.05). TAT-3L4F alone increased cytosolic pERK1/2 (p < 0.05), butnot nuclear pERK1/2. The combination of WAY163909 plus TAT-3L4F increased cytosolic pERK1/2 but not nuclear pERK1/2.

Conclusions: These data suggest that disruption of 5-HT2CR:PTEN complex shifts the profile of agonist-induced pERK1/2and represents a neurobiological mechanism which is under inter-rogation for the development of pharmacological treatments fordisorders with disrupted 5-HT2CR signaling.

Financial support: DA030977.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.651