Active vaccination inhibits the acquisition of methamphetamine self-administration in rats

s / Drug and Alcohol Dependence 140 (2014) e86–e168 e151 Active vaccination inhibits the acquisition of methamphetamine self-administration in rats Michelle L. Miller1, A.Y. Moreno2, S. Aarde1, K. Creehan1, K. Janda2, Michael A. Taffe1 1 Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, United States 2 Chemistry, Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, United States Aims: d-Methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects ofMETH. The aimof the current study was to investigate whether active vaccination against METH could alter intravenous METH self-administration in rats. Methods: Male Sprague-Dawley rats (N=24) were vaccinated with either a candidate anti-METH vaccine (MH6) or a control keyhole-limpet hemocyanin conjugate vaccine (KLH). Effects of vaccination on the acquisition of METH self-administration under 0.1mg/kg/inf and across a range of doses of METH (0, 0.01, 0.05, 0.20mg/kg/inf) during steady-state responding were investigated. Results: Active vaccination inhibited the acquisition of METH self-administration under the 0.1mg/kg/inf dose condition, with 66% of the MH6-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Conclusions: These data demonstrate that active immunopharmacotherapy for METH inhibits the acquisition of METH selfadministration. Financial support: Supported by NIH/NIDA grant #DA024705. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.426 Behavioral adjustment in prenatally cocaine-exposed adolescents Meeyoung O. Min1, S. Minnes1, E.J. Short2, S. Yoon1, L.T. Singer3 1 Applied Social Sciences, Case Western Reserve University, Cleveland, OH, United States 2 Psychology, Case Western Reserve University, Cleveland, OH, United States 3 Environmental Health, Case Western Reserve University, Cleveland, OH, United States Aims: To assess differences in self-reported behavioral adjustment in prenatally cocaine exposed (PCE) andnon-cocaine exposed (NCE) adolescents at ages 12 and 15 years. Methods: Adolescents (N=371; 189 PCE, 182 NCE), primarily African-American and low socioeconomic status, were prospectively enrolled in a longitudinal study at birth (92% retention). The Youth Self-Report (YSR) was used to assess behavioral adjustment. A mixed model repeated measures analysis was used, controlling for covariates including other prenatal drug exposures and lead. Results: Adolescents with PCE reported greater externalizing problems (adjusted mean± SE: 49.9±0.78 vs. 47.3±0.76 at 12; 52.6±0.86 vs. 50.2±0.84 at 15) than NCE adolescents (p< .02) after control for covariates. PCE adolescents reported increased inattention at 15 year (59.4±0.68 vs. 57.3±0.67; p< .03) compared to NCE adolescents. No PCE effect on internalizing problems was found. All externalizing, internalizing, and attention problem scores increased from 12 to 15 years. Girls reported a greater increase in externalizing and internalizing problems from 12 to 15 years than boys. Greater maternal psychological distress was related to higher internalizing problems (p= .03). Greater parental monitoring was related to fewer externalizing problems; greater family conflict was related to more externalizing and attention problems;andgreaterviolenceexposurewas related tomoreexternalizing and internalizing problems. Prenatal marijuana exposure was related to inattention (p< .02). Marginal effects of prenatal alcohol on internalizing behavior (p= .07) and blood lead on inattention (p= .051) were found. Conclusions: PCE is related to externalizing problems and inattention in adolescence. Interventions focusing on strengthening parental monitoring and decreasing family conflict and violence exposure may be promising in reducing behavioral problems among high risk adolescents with PCE. Financial support: National Institute onDrug AbuseGrant R0107957. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.427 Executive function in children with prenatal cocaine exposure at 12 and 15 years Sonia Minnes1, Meeyoung O. Min1, E. Short3, M. Wu1, S. Yoon1, Lynn Singer2 1 Applied Social Sciences, Case Western Reserve University, Cleveland, OH, United States 2 School of Medicine, Case Western Reserve University, Cleveland, OH, United States 3 Psychology, Case Western Reserve University, Cleveland, OH, United States Aims: To examine between and within group differences in executive function (EF) in prenatally cocaine exposed (PCE) and non-cocaine exposed (NCE) children at 12 and 15 years of age. Methods: Three hundred seventy (188 PCE, 182 NCE), primarily African American, low socioeconomic status children participated in a prospective, longitudinal study. The Behavior Rating Inventory of Executive Function (BRIEF) Parent Form was administered to assess executive function (EF). Broadband T-scores for Behavioral Regulation (BRI), Metacognition (MCI) and Global (GEF) were assessed. A mixed model repeated measures analysis was used, controlling for covariates including other prenatal drug exposures and environmental factors. These analyses were completed separately for males and female based on previous cohort findings. Results: PCE females showed greater behavioral regulation problems compared to NCE females at 12 years (adjusted mean: 55.45 vs. 50.01, p= .002). There was a significant time effect for PCE girls (p< .04) and boys (p< .05) indicating fewer behavioral regulation problems over time. Therewere no cocaine effects for boys. For MCI and GEF, there were significant cocaine effects among females at 12 (p< .001) and 15 (p< .04), and a significant time effect for PCE girls (p< .03). A significant negative effect of prenatal alcohol exposure was noted for both males and females on MCI and GEF. Conclusions: PCE is associatedwith increasedproblemsof executive function among females only at 12 and 15 years of age. Prenatal alcohol exposure is negatively associated with MCI and GEF. Developing interventions aimed at improving behavioral regulations andmetacognitive ability warrant attention for prenatally cocaine exposed females and alcohol exposed individuals of both genders. Financial support: This researchwas supported by theNational Institute on Drug Abuse grant (NIDA R0107957). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.428