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Delay discounting of remifentanil under a drug–drug choice procedure
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Abstracts / Drug and Alcohol Dependence 140 (2014) e86–e168
Delay discounting of remifentanil under a drug–drug choice procedure David R. Maguire, L.R. Gerak, C.P. France Pharmacology, UTHSCSA, San Antonio, TX, United States Aims: A drug-versus-drug choice procedure was used to examine the impact of reinforcement delay on responding maintained by the mu opioid receptor agonist remifentanil. Methods: Rhesus monkeys (n = 4) lever pressed under a concurrent fixed-ratio 30 schedule. Responses on either lever delivered an i.v. infusion, either remifentanil or saline. After dose–effect curves were determined when remifentanil was available on one lever and saline was available on the other, monkeys chose between two doses of remifentanil, and the delay to delivery of the larger dose was varied systematically across sessions. Results: Remifentanil (0.01–1.0 g/kg/infusion) dose dependently increased responding on the drug lever when the alternative was saline. When given a choice between two doses of remifentanil that maintained responding, monkeys chose the larger dose. When given a choice between a smaller dose delivered immediately (0.032–0.01 g/kg), and a larger dose (0.32–1.0 g/kg) delivered after a delay (30–240 s), responding for the larger dose decreased, and responding for the smaller dose increased, as a function of delay. Conclusions: Responding under this choice procedure was sensitive to both reinforcer amount and delay. In some cases, when the larger dose was delayed, monkeys responded for smaller doses of remifentanil that otherwise (i.e., during the single-lever selfadministration study) did not maintain levels of responding above that maintained by saline, suggesting that the context in which drug taking occurs (e.g., changes in the availability of other reinforcers) can influence the reinforcing effectiveness of drugs. The imposition of a delay not only reduces the value of the delayed reinforcers but also increases the relative value of other immediately available commodities (e.g., smaller doses of drug). Enhancement of the reinforcing effectiveness of drugs in the context of other delayed reinforcers might contribute to increased vulnerability for drug abuse among individuals that are more sensitive to reinforcer delay. Financial support: Supported by USPHS Grants R01DA029254, K05DA017918 (CPF), and T32DA031115 (DRM). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.375 State versus trait: Evaluating the stability of neurocognitive functioning over time in cocaine-dependent participants James J. Mahoney 1,2 , A.D. Kalechstein 1,2 , Thomas F. Newton 1,2 , S. Meyer 1,2 , C. Verrico 1,2 , R. Bennett 1,2 , L. Chang 1,2 , Richard De La Garza II 1,2 1 2
Psychiatry, BCM, Houston, TX, United States Psychiatry, MEDVAMC, Houston, TX, United States
Aims: The goal of this project was to evaluate whether neurocognitive functioning remains stable, improves, or worsens over time in non-treatment seeking cocaine-dependent participants. Methods: Using a within-subjects study design, participants were administered the following neurocognitive tests at 3 distinct time points (study visits): Continuous Performance Task (CPT; a measure of attention/information processing), N-Back (a measure of working memory), Hopkins Verbal Learning Task-Revised (HVLT-R; a measure of verbal memory), and the Wechsler Adult Intelligence Scale (a measure of IQ). The order of administration was
the same and the assessments were identical with the exception of the HVLT where alternate forms were administered. Results: The sample (N = 22) included cocaine-dependent volunteers who were primarily African-American males aged 44.0 ± 1.1 (mean ± SEM) years. Participants reported using 2.2 ± 0.6 grams of cocaine/day, 17.1 ± 1.9 days out of the last 30 days, and an average of 17.7 ± 1.1 years of use. On average, 117.4 ± 15.5 days elapsed between the administration of the first and second neurocognitive batteries, and 135.2 ± 29.4 days elapsed between the second and third neurocognitive batteries. With regard to the HVLTand N-Back assessments, performance did not significantly differ across the 3 assessments. However, performance worsened over time and/or were variable between sessions for a few CPT indices, including number of omissions, variability, hit rate standard error, and hit rate block change. Conclusions: Performance on measures of neurocognition, particularly episodic and working memory, appear to be consistent over time. These findings reflect, in the absence of any intervention or other acute event, stability of neurocognition in this cohort. Furthermore, with respect to the psychometric properties of the battery, the results show that these assessments are not susceptible to practice effects. Financial support: This work was conducted at the MEDVAMC, Houston, TX. Funding from NIH grants: DA023624; DA028387; DA023588. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.376 Poorer parental monitoring is associated with cocaine exposure in early adolescence in girls but not boys Elana Mansoor 1 , Veronica H. Accornero 1 , J.C. Anthony 2 , L. Xue 1 , C. Morrow 1 , E. Bandstra 1 1 Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States 2 Epidemiology, Michigan State University, East Lansing, MI, United States
Aims: To study the degree to which early adolescent cocaine exposure (EACE) is associated with parental monitoring (PM), with attention to male-female differences and holding constant prenatal cocaine exposure (PCE). Methods: Participants were enrolled at birth in the longitudinal Miami Prenatal Cocaine Study. As part of the 12-year follow-up exam, 204 girls (114 PCE) and 198 boys (95 PCE) were studied. PCE was assessed by maternal self-report and drug assays; EACE solely by drug assays. Log odds of EACE have been regressed on self-report caregiver PM, based on standard multi-item scales, with PCE, male sex, and other covariates. Results: Higher PM levels, as measured by caregiver report, predicted EACE for early adolescent females (p < 0.05), but not for males (p > 0.05), with PCE and other covariates held constant. This was not the case when the early adolescents reported on PM. Conclusions: EACE assessment via bioassay, and not by child or parent report, is a strength and lends credence to the observed association. It is possible to speculate that the relationship is predictive and not merely correlational, but firm conclusions cannot be drawn about cause-effect relations. Financial support: ORWH/NIDA P50 DA 024584; NIDA R01 DA 006556, K01 DA 016720, K05DA15799. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.377
Abstracts / Drug and Alcohol Dependence 140 (2014) e86–e168
Delay discounting of remifentanil under a drug–drug choice procedure David R. Maguire, L.R. Gerak, C.P. France Pharmacology, UTHSCSA, San Antonio, TX, United States Aims: A drug-versus-drug choice procedure was used to examine the impact of reinforcement delay on responding maintained by the mu opioid receptor agonist remifentanil. Methods: Rhesus monkeys (n = 4) lever pressed under a concurrent fixed-ratio 30 schedule. Responses on either lever delivered an i.v. infusion, either remifentanil or saline. After dose–effect curves were determined when remifentanil was available on one lever and saline was available on the other, monkeys chose between two doses of remifentanil, and the delay to delivery of the larger dose was varied systematically across sessions. Results: Remifentanil (0.01–1.0 g/kg/infusion) dose dependently increased responding on the drug lever when the alternative was saline. When given a choice between two doses of remifentanil that maintained responding, monkeys chose the larger dose. When given a choice between a smaller dose delivered immediately (0.032–0.01 g/kg), and a larger dose (0.32–1.0 g/kg) delivered after a delay (30–240 s), responding for the larger dose decreased, and responding for the smaller dose increased, as a function of delay. Conclusions: Responding under this choice procedure was sensitive to both reinforcer amount and delay. In some cases, when the larger dose was delayed, monkeys responded for smaller doses of remifentanil that otherwise (i.e., during the single-lever selfadministration study) did not maintain levels of responding above that maintained by saline, suggesting that the context in which drug taking occurs (e.g., changes in the availability of other reinforcers) can influence the reinforcing effectiveness of drugs. The imposition of a delay not only reduces the value of the delayed reinforcers but also increases the relative value of other immediately available commodities (e.g., smaller doses of drug). Enhancement of the reinforcing effectiveness of drugs in the context of other delayed reinforcers might contribute to increased vulnerability for drug abuse among individuals that are more sensitive to reinforcer delay. Financial support: Supported by USPHS Grants R01DA029254, K05DA017918 (CPF), and T32DA031115 (DRM). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.375 State versus trait: Evaluating the stability of neurocognitive functioning over time in cocaine-dependent participants James J. Mahoney 1,2 , A.D. Kalechstein 1,2 , Thomas F. Newton 1,2 , S. Meyer 1,2 , C. Verrico 1,2 , R. Bennett 1,2 , L. Chang 1,2 , Richard De La Garza II 1,2 1 2
Psychiatry, BCM, Houston, TX, United States Psychiatry, MEDVAMC, Houston, TX, United States
Aims: The goal of this project was to evaluate whether neurocognitive functioning remains stable, improves, or worsens over time in non-treatment seeking cocaine-dependent participants. Methods: Using a within-subjects study design, participants were administered the following neurocognitive tests at 3 distinct time points (study visits): Continuous Performance Task (CPT; a measure of attention/information processing), N-Back (a measure of working memory), Hopkins Verbal Learning Task-Revised (HVLT-R; a measure of verbal memory), and the Wechsler Adult Intelligence Scale (a measure of IQ). The order of administration was
the same and the assessments were identical with the exception of the HVLT where alternate forms were administered. Results: The sample (N = 22) included cocaine-dependent volunteers who were primarily African-American males aged 44.0 ± 1.1 (mean ± SEM) years. Participants reported using 2.2 ± 0.6 grams of cocaine/day, 17.1 ± 1.9 days out of the last 30 days, and an average of 17.7 ± 1.1 years of use. On average, 117.4 ± 15.5 days elapsed between the administration of the first and second neurocognitive batteries, and 135.2 ± 29.4 days elapsed between the second and third neurocognitive batteries. With regard to the HVLTand N-Back assessments, performance did not significantly differ across the 3 assessments. However, performance worsened over time and/or were variable between sessions for a few CPT indices, including number of omissions, variability, hit rate standard error, and hit rate block change. Conclusions: Performance on measures of neurocognition, particularly episodic and working memory, appear to be consistent over time. These findings reflect, in the absence of any intervention or other acute event, stability of neurocognition in this cohort. Furthermore, with respect to the psychometric properties of the battery, the results show that these assessments are not susceptible to practice effects. Financial support: This work was conducted at the MEDVAMC, Houston, TX. Funding from NIH grants: DA023624; DA028387; DA023588. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.376 Poorer parental monitoring is associated with cocaine exposure in early adolescence in girls but not boys Elana Mansoor 1 , Veronica H. Accornero 1 , J.C. Anthony 2 , L. Xue 1 , C. Morrow 1 , E. Bandstra 1 1 Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States 2 Epidemiology, Michigan State University, East Lansing, MI, United States
Aims: To study the degree to which early adolescent cocaine exposure (EACE) is associated with parental monitoring (PM), with attention to male-female differences and holding constant prenatal cocaine exposure (PCE). Methods: Participants were enrolled at birth in the longitudinal Miami Prenatal Cocaine Study. As part of the 12-year follow-up exam, 204 girls (114 PCE) and 198 boys (95 PCE) were studied. PCE was assessed by maternal self-report and drug assays; EACE solely by drug assays. Log odds of EACE have been regressed on self-report caregiver PM, based on standard multi-item scales, with PCE, male sex, and other covariates. Results: Higher PM levels, as measured by caregiver report, predicted EACE for early adolescent females (p < 0.05), but not for males (p > 0.05), with PCE and other covariates held constant. This was not the case when the early adolescents reported on PM. Conclusions: EACE assessment via bioassay, and not by child or parent report, is a strength and lends credence to the observed association. It is possible to speculate that the relationship is predictive and not merely correlational, but firm conclusions cannot be drawn about cause-effect relations. Financial support: ORWH/NIDA P50 DA 024584; NIDA R01 DA 006556, K01 DA 016720, K05DA15799. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.377