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High genetic risk for methamphetamine intake in mice relates to perturbations in neurotransmission in medial prefrontal cortex and nucleus accumbens
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Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Serum concentrations of BDNF during the immediate puerperium among women with crack dependence in comparison to healthy mothers: Preliminary data Claudia Szobot 2,3,4 , V. Mardini 1,3,4 , F. Pechansky 1,3 , F. Kapczinski 1,5 , K.M. Cereser 1,5 , G. Fries 5 , N. Canabarro 2 , L. Manna 2 , R. Parcianello 2 , M. Zavaschi 1 , F. Rosa 3 , L. Pereira 3 , L.A. Rohde 1,4 1
UFRGS, Porto Alegre, Brazil ULBRA, Canoas, Brazil 3 Research Center on Alcohol and Drugs, HCPA, Porto Alegre, Brazil 4 ADHD Outpatient Clinic, HCPA, Porto Alegre, Brazil 5 Laboratório de Psiquiatria Molecular, HCPA, Porto Alegre, Brazil 2
Aims: The use of crack probably is experimented by the organism as something toxic, activating protective responses, like those mediated by Brain-Derived Neurotrophic Factor (BDNF). During pregnancy there are changes in immune system, such as in stress response, and some psychiatric disorders change their profile during or after pregnancy. The goal of this study was to compare serum levels of BDNF during the immediate puerperium among women with crack use vs healthy mothers Methods: Study of a series of cases. Serum concentrations of BDNF during the immediate puerperium was compared among women with crack dependence, recruited at two large hospital, vs healthy mothers, derived by mothers who accepted to donate the cord blood of their babies to Bank Umbilical Cord Blood and Placenta of our institution. The levels of BDNF were measured in peripheral blood. Results: The sample was comprised by 29 women with crack dependence and 29 healthy mothers. In the crack group there were more single mothers (33.3% vs zero, p = 0.001) and non-white ethnicity (76.5% vs 23.1%, p = 0.001). BDNF level at the delivery time was significantly higher among women who consumed crack during pregnancy (median = 44.86) in comparison to non-drug addicts (median 28.11. Mann-Whitney U = 285, Z = −2.17, p = 0.035). Conclusions: To the best of our knowledge, this is the first study that documents the BDNF levels in women who were users of crack during pregnancy measured in peripheral blood after delivery. It seems that the process of adaptive increased of BDNF in order to seek a neuronal survival, caused by crack consumption, is kept under pregnancy conditions. Financial support: SENAD and CAPES, Brazil. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.615 High genetic risk for methamphetamine intake in mice relates to perturbations in neurotransmission in medial prefrontal cortex and nucleus accumbens Karen K. Szumlinski 1 , D. Maliniak 1 , M.G. Wroten 1 , P.N. Ruiz 1 , K.D. Lominac 1 , T.J. Phillips 2 1 University of California Santa Barbara, Santa Barbara, CA, United States 2 Oregon Health Sciences University, Portland, OR, United States
Aims: The recent creation of methamphetamine (MA) high and low drinking (MAHDR and MALDR) selected lines of mice that also exhibit high versus low sensitivity to MA reward enable the exploration of the neural underpinnings of genetic risk for MA addiction.
Thus, this study aimed to relate genotypic differences in MA reward to extracellular levels of neurotransmitters within the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). Methods: In vivo microdialysis was used to quantify basal levels of serotonin, dopamine and glutamate, as well as the capacity of a 2 mg/kg MA injection to elevate neurotransmitter levels, in female mice from the MAHDR and MALDR selected lines, as well as female mice from the F2 cross of the C57BL/6J and DBA2/J inbred strains (B6D2F2). Results: Genotypic differences in basal extracellular neurotransmitters were observed for mPFC and NAC dopamine (MAHDR < MALDR = D2B6, for mPFC and NAC glutamate (MALDR < MAHDR = D2B6) and for NAC serotonin (MAHDR > MALDR = D2B6). Genotype differences were also observed regarding MA-stimulated neurotransmitter release for mPFC dopamine (MAHDR > MALDR = B6D2), mPFC serotonin (MAHDR < MALDR = B6D2) and NAC glutamate (MALDR < MAHDR = B6D2). Conclusions: Together, these data indicate perturbations in both monoaminergic and glutamatergic systems within the corticoaccumbens pathway as genetic correlates of a high MAconsuming phenotype. Financial support: This work was supported, in part, by NIDA grant R01DA024038 to KKS, the Department of Veterans Affairs and NIDA grant P50 DA018165 to TJP. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.616 Neural tracking of prediction error (PE) is reduced in substance-dependent individuals Jody Tanabe 1 , J. Reynolds 3 , T. Krmpotich 1 , E. Claus 4 , L. Thompson 1 , Y. Du 1 , M. Banich 2 1
University of Colorado Denver School of Medicine, Denver, CO, United States 2 University of Colorado Boulder, Boulder, CO, United States 3 University of Denver, Denver, CO, United States 4 The Mind Research Network, Albuquerque, NM, United States Aims: Substance dependent individuals (SDI) make poor decisions on the Iowa Gambling Task (IGT), a task that simulates real-life decisions involving risk and uncertainty. Decision-making depends upon several factors, including how sensitive individuals are to feedback and how well they learn based on such feedback. A physiological signal, driven by striatal dopamine, that guides learning and decision-making based on feedback is prediction error (PE). Hypothesis: Compared to controls, SDI would show alterations in the neural tracking of PE during decision-making on a modified IGT (mIGT). Methods: Thirty-two SDI and 30 controls played the mIGT during fMRI scanning. Behavior was analyzed using a cognitive model which identifies psychological processes underlying IGT performance (Stout et al., 2004). For each trial, the model computes a prediction error (PE), the difference between predicted and expected outcome. Tracking of PE was compared across group using a 2-sample t-test. Statistical threshold was set at voxel-level of p < 0.005, uncorrected, and p < 0.01 whole-brain cluster-corrected, corresponding to an extent threshold of 39 voxels based on 10,000 Monte Carlo simulations. Results: Consistent with previous work on the IGT, the cognitive model parameters indicated that compared to controls, SDI made more erratic choices (p = 0.02) and demonstrated a trend toward lower sensitivity to loss (p = 0.06) on the mIGT. SDI did not track
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Serum concentrations of BDNF during the immediate puerperium among women with crack dependence in comparison to healthy mothers: Preliminary data Claudia Szobot 2,3,4 , V. Mardini 1,3,4 , F. Pechansky 1,3 , F. Kapczinski 1,5 , K.M. Cereser 1,5 , G. Fries 5 , N. Canabarro 2 , L. Manna 2 , R. Parcianello 2 , M. Zavaschi 1 , F. Rosa 3 , L. Pereira 3 , L.A. Rohde 1,4 1
UFRGS, Porto Alegre, Brazil ULBRA, Canoas, Brazil 3 Research Center on Alcohol and Drugs, HCPA, Porto Alegre, Brazil 4 ADHD Outpatient Clinic, HCPA, Porto Alegre, Brazil 5 Laboratório de Psiquiatria Molecular, HCPA, Porto Alegre, Brazil 2
Aims: The use of crack probably is experimented by the organism as something toxic, activating protective responses, like those mediated by Brain-Derived Neurotrophic Factor (BDNF). During pregnancy there are changes in immune system, such as in stress response, and some psychiatric disorders change their profile during or after pregnancy. The goal of this study was to compare serum levels of BDNF during the immediate puerperium among women with crack use vs healthy mothers Methods: Study of a series of cases. Serum concentrations of BDNF during the immediate puerperium was compared among women with crack dependence, recruited at two large hospital, vs healthy mothers, derived by mothers who accepted to donate the cord blood of their babies to Bank Umbilical Cord Blood and Placenta of our institution. The levels of BDNF were measured in peripheral blood. Results: The sample was comprised by 29 women with crack dependence and 29 healthy mothers. In the crack group there were more single mothers (33.3% vs zero, p = 0.001) and non-white ethnicity (76.5% vs 23.1%, p = 0.001). BDNF level at the delivery time was significantly higher among women who consumed crack during pregnancy (median = 44.86) in comparison to non-drug addicts (median 28.11. Mann-Whitney U = 285, Z = −2.17, p = 0.035). Conclusions: To the best of our knowledge, this is the first study that documents the BDNF levels in women who were users of crack during pregnancy measured in peripheral blood after delivery. It seems that the process of adaptive increased of BDNF in order to seek a neuronal survival, caused by crack consumption, is kept under pregnancy conditions. Financial support: SENAD and CAPES, Brazil. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.615 High genetic risk for methamphetamine intake in mice relates to perturbations in neurotransmission in medial prefrontal cortex and nucleus accumbens Karen K. Szumlinski 1 , D. Maliniak 1 , M.G. Wroten 1 , P.N. Ruiz 1 , K.D. Lominac 1 , T.J. Phillips 2 1 University of California Santa Barbara, Santa Barbara, CA, United States 2 Oregon Health Sciences University, Portland, OR, United States
Aims: The recent creation of methamphetamine (MA) high and low drinking (MAHDR and MALDR) selected lines of mice that also exhibit high versus low sensitivity to MA reward enable the exploration of the neural underpinnings of genetic risk for MA addiction.
Thus, this study aimed to relate genotypic differences in MA reward to extracellular levels of neurotransmitters within the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). Methods: In vivo microdialysis was used to quantify basal levels of serotonin, dopamine and glutamate, as well as the capacity of a 2 mg/kg MA injection to elevate neurotransmitter levels, in female mice from the MAHDR and MALDR selected lines, as well as female mice from the F2 cross of the C57BL/6J and DBA2/J inbred strains (B6D2F2). Results: Genotypic differences in basal extracellular neurotransmitters were observed for mPFC and NAC dopamine (MAHDR < MALDR = D2B6, for mPFC and NAC glutamate (MALDR < MAHDR = D2B6) and for NAC serotonin (MAHDR > MALDR = D2B6). Genotype differences were also observed regarding MA-stimulated neurotransmitter release for mPFC dopamine (MAHDR > MALDR = B6D2), mPFC serotonin (MAHDR < MALDR = B6D2) and NAC glutamate (MALDR < MAHDR = B6D2). Conclusions: Together, these data indicate perturbations in both monoaminergic and glutamatergic systems within the corticoaccumbens pathway as genetic correlates of a high MAconsuming phenotype. Financial support: This work was supported, in part, by NIDA grant R01DA024038 to KKS, the Department of Veterans Affairs and NIDA grant P50 DA018165 to TJP. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.616 Neural tracking of prediction error (PE) is reduced in substance-dependent individuals Jody Tanabe 1 , J. Reynolds 3 , T. Krmpotich 1 , E. Claus 4 , L. Thompson 1 , Y. Du 1 , M. Banich 2 1
University of Colorado Denver School of Medicine, Denver, CO, United States 2 University of Colorado Boulder, Boulder, CO, United States 3 University of Denver, Denver, CO, United States 4 The Mind Research Network, Albuquerque, NM, United States Aims: Substance dependent individuals (SDI) make poor decisions on the Iowa Gambling Task (IGT), a task that simulates real-life decisions involving risk and uncertainty. Decision-making depends upon several factors, including how sensitive individuals are to feedback and how well they learn based on such feedback. A physiological signal, driven by striatal dopamine, that guides learning and decision-making based on feedback is prediction error (PE). Hypothesis: Compared to controls, SDI would show alterations in the neural tracking of PE during decision-making on a modified IGT (mIGT). Methods: Thirty-two SDI and 30 controls played the mIGT during fMRI scanning. Behavior was analyzed using a cognitive model which identifies psychological processes underlying IGT performance (Stout et al., 2004). For each trial, the model computes a prediction error (PE), the difference between predicted and expected outcome. Tracking of PE was compared across group using a 2-sample t-test. Statistical threshold was set at voxel-level of p < 0.005, uncorrected, and p < 0.01 whole-brain cluster-corrected, corresponding to an extent threshold of 39 voxels based on 10,000 Monte Carlo simulations. Results: Consistent with previous work on the IGT, the cognitive model parameters indicated that compared to controls, SDI made more erratic choices (p = 0.02) and demonstrated a trend toward lower sensitivity to loss (p = 0.06) on the mIGT. SDI did not track