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Coffee and energy drink use in college freshmen: Is trouble brewing?
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Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117
Long-acting injectable naltrexone induction: A randomized trial of outpatient opioid detoxification with naltrexone vs. buprenorphine Maria A. Sullivan, A. Bisaga, K. Carpenter, John J. Mariani, Kaitlyn Mishlen, Edward V. Nunes Columbia University/New York State Psychiatric Institute, New York, NY, United States Aims: Antagonist therapy for opioid dependence with naltrexone, available in long-acting injectable form, represents an important but underutilized treatment option. The aims of this study are to develop procedures for outpatient detoxification and to compare induction rates onto injectable naltrexone (XR-NTX) between groups receiving naltrexone-assisted vs. buprenorphineassisted outpatient detoxification. Methods: Opioid-dependent participants seeking treatment were randomized into 2 groups for short-term outpatient opioid detoxification. One group received a 7-day buprenorphine taper, followed by a 7-day long washout and an injection of XR-NTX. A second group received a single day of buprenorphine, followed by a washout day and 4-day oral naltrexone taper and an injection of XR-NTX. Following induction, participants received behavioral therapy for 4 weeks Results: To date, 79 participants (65% white, 86% male, 34% prescription opioid users) have entered the study and were randomized to naltrexone (n = 53) or buprenorphine (n = 26) arm. 51% of participants in the naltrexone arm and 46% in the buprenorphine arm have been successfully inducted onto XR-NTX (p = .69). 50% of participants in the naltrexone arm and 36% in the buprenorphine arm completed Week 5 (p = .25) and received a second XR-NTX injection. Conclusions: The data from this study suggests that oral naltrexone is an important alternative medication useful in the opioid detoxification process. Participants treated with naltrexone during detoxification had comparable outcomes with those in the buprenorphine-assisted detoxification in becoming inducted onto XR-NTX. At least half of the patients undergoing oral naltrexone-assisted outpatient detoxification completed induction onto XR-NTX. These results suggest initiation of XR-NTX on an outpatient basis is a clinically viable treatment option that may be attractive to many patients and providers. Financial support: NIDA (DA 010746-09A1). http://dx.doi.org/10.1016/j.drugalcdep.2014.09.671 Genetic background influences the change from the discriminative stimulus to the rewarding effects of psychostimulants in rats Tsutomu Suzuki, Daisuke Aikawa, Asuka Takanohashi, Tomoya Saeki, Masahiro Shibasaki, Tomohisa Mori Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan Aims: The discriminative stimulus effects of psychostimulants are closely associated with their rewarding effects. It has been shown that Lewis (LEW) rats are more sensitive to the behavioral effects of psychostimulants than Fischer 344 (F344) rats. However, little information is available regarding the genetic background on the discriminative stimulus effects of psychostimulants. Therefore, the present study was designed to investigate the possible similarities between the sensitivity to the production of discriminative
stimulus effects and the rewarding effects of psychostimulants in LEW and F344 rats. Methods: Drug discrimination, conditioned place preference, and in vivo microdialysis studies by using LEW and F344 rats were conducted based on our previous reports. Results: In the conditioned place preference paradigm, psychostimulants produced strong rewarding effects in LEW rats, while no significant effects were seen in F344 rats. On the other hand, there was no difference in the discriminative stimulus effects as well as dopamine-releasing effects from the nucleus accumbens after psychostimulants administration between LEW and F344 rats. Furthermore, we found that the number of astrocytes in the nucleus accumbens was almost 3 times larger in LEW rats than those in F344 rats. Conclusions: These results suggest that the genetic background may influence the change from the discriminative stimulus effects of psychostimulants to their rewarding effects as the postsynaptic event in the nucleus accumbens. Financial support: This work was supported in part by Grantsin-Aid for Scientific Research from the Ministry of Health, Labor and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology of Japan. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.672 Coffee and energy drink use in college freshmen: Is trouble brewing? Dace Svikis 1 , Pamela Dillon 1 , Leroy Thacker 1 , Steven Meredith 2 , Kathryn M. Polak 1 , Danielle Dick 1 , Susan Kornstein 1 , Kenneth Kendler 1 1 Virginia Commonwealth University, Richmond, VA, United States 2 Johns Hopkins School of Medicine, Baltimore, MD, United States
Aims: Historically, daily coffee use was associated with heavy alcohol use and problems (Hull et al., 2011). More recently, caffeinecontaining energy drink (e-drink) use has escalated in college students, and e-drinks have been linked to alcohol dependence, marijuana use and risky sexual behaviors (e.g., Arria et al., 2011). The present study compared rates of alcohol/other drug use and problems in 3 groups of freshmen: those consuming coffee + edrinks (C + E); those consuming coffee but no e-drinks (C) and those consuming neither substance (NoCE). Methods: Subjects were N = 1953 freshmen at an urban university who completed a 30-min on-line survey. Survey domains included: demographics, alcohol and other drug use (including caffeine), personality and family history (Spit for Science project*). The sample was 39% male; 52% Caucasian and 20% Black. The 3 caffeine use groups included: C + E (N = 144) C (N = 883) and NoCE (N = 926) Alcohol, tobacco and other drug use and family history variables were compared across the 3 caffeine use groups controlling for race and gender, using a logistic regression model with post-hoc comparisons. Results: Relative to NoCEs, C + Es were significantly more likely to endorse 8 of 9 alcohol use disorder diagnostic symptoms. Further, C + Es endorsed 6 of the 8 alcohol symptoms at higher rates than Cs (all p < .05). For other drugs, there was also a significant difference between the 3 groups, with C + Es having the highest rates of use (6+ times) of cannabis, sedatives, stimulants, cocaine and opioids (all p < 0.002). Cigarette smoking (100+ cigs) followed the same pattern (31% E + C; 11% C and 7% NoCE; p < .0001). Finally, E + Cs were more likely to report maternal alcohol and drug and paternal drug problems than Cs and NoCEs (all p < .05).
Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117
Conclusions: While findings affirmed the association between caffeine use and alcohol/other drug use and problems, the relationship was strongest in students consuming both coffee and energy drinks. Results should inform future prevention and intervention efforts. Financial support: NIH R37 AA011408* and RO1 DA026091. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.673 Loss of serotonin (5-HT) 2C receptor (5-HT2CR) tone in the ventral tegmental area modulates cocaine-related behaviors Sarah E. Swinford-Jackson, Noelle C. Anastasio, Robert G. Fox, Sonja J. Stutz, Kathryn Cunningham Center for Addiction Research, UTMB, Galveston, TX, United States Aims: The mesocorticolimbic dopamine system is known to mediate the hyper- motive and reinforcing effects of cocaine. Serotonergic afferents to the VTA regulate dopamine transmission through the 5-HT2C R which exerts an overall inhibitory impact on VTA function. Although understudied, a few reports identified a role for VTA 5-HT2C R signaling such that intra-VTA microinfusion of a 5-HT2C R agonist has been shown to decrease cocaine-evoked hyperactivity and cocaine self-administration. Here, we employ a virally-mediated genetic knock- down strategy to expand upon these observations and test the hypothesis that diminished VTA 5-HT2C R tone alters cocaine-related behaviors. Methods: Male Sprague-Dawley rats were evaluated for basal motor activity and cocaine-evoked hyperactivity following genetic knockdown of 5-HT2C R in the VTA. We assessed hyperactivity after an injection of cocaine (10 mg/kg, i.p.) in VTA 5-HT2C R knockdown and control rats. Rats were then trained in daily 3-h sessions to self-administer a low dose (0.25 mg/kg/inf) of cocaine on an FR1-5 schedule; the cocaine dose-response (0.05, 0.125, 0.25 and 0.75 mg/kg/inf) relationship was then evaluated to interrogate differences in sensitivity to cocaine. Results: Rats with genetic knockdown of the 5-HT2C R in the VTA displayed enhanced cocaine-evoked hyperactivity (p < 0.05) but no difference in basal loco-motion relative to control rats. There was no difference in acquisition of cocaine self-administration or infusions earned during the cocaine dose-response sessions between VTA 5-HT2C R knockdown and control rats. Conclusions: These data suggest reduced VTA 5-HT2C R tone confers an increased sensitivity to the hypermotive response but not the reinforcing properties of cocaine. Investigation into the role of VTA 5-HT2C R tone on other cocaine-related behaviors, such as motivation to respond for cocaine or cocaine cue reactivity, are underway and will provide further insight into which facets of responsivity to cocaine are modulated by 5-HT2C R function in the VTA. Financial support: DA035620, DA06511, DA024157, DA033935, DA033374. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.674
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Effects of intramuscular and oral buspirone on physiology and behavior in monkeys Kendall T. Szeliga, Susan E. Martelle, Michael A. Nader Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, United States Aims: Buspirone has multiple actions in the brain including dopamine (DA) D2-like receptor antagonism. Recent data suggest that buspirone has higher affinity at the DA D3 receptor (DAD3) compared to the DA D2 receptor (DAD2) subtype; DAD3 has been a target for medications to treat drug addiction. One behavioral assay that has been used to assess DAD3 and DAD2 involves administration of the D2-like agonist quinpirole (QUIN). QUIN elicits yawning and the ascending limb of the dose-response curve is thought to be DAD3 mediated, while higher doses of QUIN result in fewer yawns and in hypothermia; the latter is thought to be DAD2 mediated. The goal of this study was to examine, in separate groups of monkeys, the effects of buspirone administered by different routes on behavior (QUIN-elicited yawning) and physiology (QUIN-induced hypothermia). Methods: In drug-naïve male rhesus monkeys (n = 3), QUIN (0.01–0.3 mg/kg, i.m.) elicited yawning that was characterized as an inverted U-shaped function of dose, with peak yawning following 0.1 mg/kg QUIN. In a second study, drug-naïve female cynomolgus monkeys (n = 4) were surgically implanted with indwelling telemetry transmitters (D70-PCT; Data Sciences International, St. Paul, MN). QUIN (0.1 mg/kg, i.m.) induced significant hypothermia. Results: Irrespective of route, buspirone (0.1, i.m. and 0.3–1.0 mg/kg, p.o.) attenuated 0.1 mg/kg QUIN-elicited yawning. Intramuscular (0.1–0.56 mg/kg) but not oral (1.0–5.6 mg/kg) buspirone attenuated QUIN-induced hypothermia. Conclusions: The present data support the hypothesis that oral buspirone is primarily a DAD3 antagonist. If DAD3 is a viable target for addiction medications, then additional studies using oral buspirone are warranted. Financial support: DA012460 and DA010584. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.675 Lower oxidative stress in umbilical blood cord of newborns exposed to crack during pregnancy Claudia M. Szobot 1 , Maria Zavaschi 1 , V. Mardini 1 , F. Kapczinski 1 , Márcia Kauer-Sant’anna 1 , Gabriela Colpo 1 , Bianca Aguiar 1 , Gabrielle Cunha 1 , L. Manna 1 , Anna Rose Childress 2 , Daniel Langleben 2 , K.M. Cereser 1 , L.A. Rohde 1 1 Federal University of Rio Grande do Sul, Porto Alegre, Brazil 2 Treatment Research Center, Philadelphia, PA, United States
Aims: The use of crack-cocaine is a major health concern in several countries. Among its users, pregnant women and their newborns, exposed to crack-cocaine intrautero, deserve special attention. One of the toxic mechanisms of crack-cocaine consists of oxidative stress (OS), which plays an important role in the embryonic development, neonatal and pregnancy-related disorders. Little is known about OS in babies exposed to crack-cocaine during pregnancy. The aim of this study was to compare the levels of OS in newborns exposed to crack during pregnancy (EN) and nonexposed newborns (NEN).
Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117
Long-acting injectable naltrexone induction: A randomized trial of outpatient opioid detoxification with naltrexone vs. buprenorphine Maria A. Sullivan, A. Bisaga, K. Carpenter, John J. Mariani, Kaitlyn Mishlen, Edward V. Nunes Columbia University/New York State Psychiatric Institute, New York, NY, United States Aims: Antagonist therapy for opioid dependence with naltrexone, available in long-acting injectable form, represents an important but underutilized treatment option. The aims of this study are to develop procedures for outpatient detoxification and to compare induction rates onto injectable naltrexone (XR-NTX) between groups receiving naltrexone-assisted vs. buprenorphineassisted outpatient detoxification. Methods: Opioid-dependent participants seeking treatment were randomized into 2 groups for short-term outpatient opioid detoxification. One group received a 7-day buprenorphine taper, followed by a 7-day long washout and an injection of XR-NTX. A second group received a single day of buprenorphine, followed by a washout day and 4-day oral naltrexone taper and an injection of XR-NTX. Following induction, participants received behavioral therapy for 4 weeks Results: To date, 79 participants (65% white, 86% male, 34% prescription opioid users) have entered the study and were randomized to naltrexone (n = 53) or buprenorphine (n = 26) arm. 51% of participants in the naltrexone arm and 46% in the buprenorphine arm have been successfully inducted onto XR-NTX (p = .69). 50% of participants in the naltrexone arm and 36% in the buprenorphine arm completed Week 5 (p = .25) and received a second XR-NTX injection. Conclusions: The data from this study suggests that oral naltrexone is an important alternative medication useful in the opioid detoxification process. Participants treated with naltrexone during detoxification had comparable outcomes with those in the buprenorphine-assisted detoxification in becoming inducted onto XR-NTX. At least half of the patients undergoing oral naltrexone-assisted outpatient detoxification completed induction onto XR-NTX. These results suggest initiation of XR-NTX on an outpatient basis is a clinically viable treatment option that may be attractive to many patients and providers. Financial support: NIDA (DA 010746-09A1). http://dx.doi.org/10.1016/j.drugalcdep.2014.09.671 Genetic background influences the change from the discriminative stimulus to the rewarding effects of psychostimulants in rats Tsutomu Suzuki, Daisuke Aikawa, Asuka Takanohashi, Tomoya Saeki, Masahiro Shibasaki, Tomohisa Mori Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan Aims: The discriminative stimulus effects of psychostimulants are closely associated with their rewarding effects. It has been shown that Lewis (LEW) rats are more sensitive to the behavioral effects of psychostimulants than Fischer 344 (F344) rats. However, little information is available regarding the genetic background on the discriminative stimulus effects of psychostimulants. Therefore, the present study was designed to investigate the possible similarities between the sensitivity to the production of discriminative
stimulus effects and the rewarding effects of psychostimulants in LEW and F344 rats. Methods: Drug discrimination, conditioned place preference, and in vivo microdialysis studies by using LEW and F344 rats were conducted based on our previous reports. Results: In the conditioned place preference paradigm, psychostimulants produced strong rewarding effects in LEW rats, while no significant effects were seen in F344 rats. On the other hand, there was no difference in the discriminative stimulus effects as well as dopamine-releasing effects from the nucleus accumbens after psychostimulants administration between LEW and F344 rats. Furthermore, we found that the number of astrocytes in the nucleus accumbens was almost 3 times larger in LEW rats than those in F344 rats. Conclusions: These results suggest that the genetic background may influence the change from the discriminative stimulus effects of psychostimulants to their rewarding effects as the postsynaptic event in the nucleus accumbens. Financial support: This work was supported in part by Grantsin-Aid for Scientific Research from the Ministry of Health, Labor and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology of Japan. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.672 Coffee and energy drink use in college freshmen: Is trouble brewing? Dace Svikis 1 , Pamela Dillon 1 , Leroy Thacker 1 , Steven Meredith 2 , Kathryn M. Polak 1 , Danielle Dick 1 , Susan Kornstein 1 , Kenneth Kendler 1 1 Virginia Commonwealth University, Richmond, VA, United States 2 Johns Hopkins School of Medicine, Baltimore, MD, United States
Aims: Historically, daily coffee use was associated with heavy alcohol use and problems (Hull et al., 2011). More recently, caffeinecontaining energy drink (e-drink) use has escalated in college students, and e-drinks have been linked to alcohol dependence, marijuana use and risky sexual behaviors (e.g., Arria et al., 2011). The present study compared rates of alcohol/other drug use and problems in 3 groups of freshmen: those consuming coffee + edrinks (C + E); those consuming coffee but no e-drinks (C) and those consuming neither substance (NoCE). Methods: Subjects were N = 1953 freshmen at an urban university who completed a 30-min on-line survey. Survey domains included: demographics, alcohol and other drug use (including caffeine), personality and family history (Spit for Science project*). The sample was 39% male; 52% Caucasian and 20% Black. The 3 caffeine use groups included: C + E (N = 144) C (N = 883) and NoCE (N = 926) Alcohol, tobacco and other drug use and family history variables were compared across the 3 caffeine use groups controlling for race and gender, using a logistic regression model with post-hoc comparisons. Results: Relative to NoCEs, C + Es were significantly more likely to endorse 8 of 9 alcohol use disorder diagnostic symptoms. Further, C + Es endorsed 6 of the 8 alcohol symptoms at higher rates than Cs (all p < .05). For other drugs, there was also a significant difference between the 3 groups, with C + Es having the highest rates of use (6+ times) of cannabis, sedatives, stimulants, cocaine and opioids (all p < 0.002). Cigarette smoking (100+ cigs) followed the same pattern (31% E + C; 11% C and 7% NoCE; p < .0001). Finally, E + Cs were more likely to report maternal alcohol and drug and paternal drug problems than Cs and NoCEs (all p < .05).
Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117
Conclusions: While findings affirmed the association between caffeine use and alcohol/other drug use and problems, the relationship was strongest in students consuming both coffee and energy drinks. Results should inform future prevention and intervention efforts. Financial support: NIH R37 AA011408* and RO1 DA026091. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.673 Loss of serotonin (5-HT) 2C receptor (5-HT2CR) tone in the ventral tegmental area modulates cocaine-related behaviors Sarah E. Swinford-Jackson, Noelle C. Anastasio, Robert G. Fox, Sonja J. Stutz, Kathryn Cunningham Center for Addiction Research, UTMB, Galveston, TX, United States Aims: The mesocorticolimbic dopamine system is known to mediate the hyper- motive and reinforcing effects of cocaine. Serotonergic afferents to the VTA regulate dopamine transmission through the 5-HT2C R which exerts an overall inhibitory impact on VTA function. Although understudied, a few reports identified a role for VTA 5-HT2C R signaling such that intra-VTA microinfusion of a 5-HT2C R agonist has been shown to decrease cocaine-evoked hyperactivity and cocaine self-administration. Here, we employ a virally-mediated genetic knock- down strategy to expand upon these observations and test the hypothesis that diminished VTA 5-HT2C R tone alters cocaine-related behaviors. Methods: Male Sprague-Dawley rats were evaluated for basal motor activity and cocaine-evoked hyperactivity following genetic knockdown of 5-HT2C R in the VTA. We assessed hyperactivity after an injection of cocaine (10 mg/kg, i.p.) in VTA 5-HT2C R knockdown and control rats. Rats were then trained in daily 3-h sessions to self-administer a low dose (0.25 mg/kg/inf) of cocaine on an FR1-5 schedule; the cocaine dose-response (0.05, 0.125, 0.25 and 0.75 mg/kg/inf) relationship was then evaluated to interrogate differences in sensitivity to cocaine. Results: Rats with genetic knockdown of the 5-HT2C R in the VTA displayed enhanced cocaine-evoked hyperactivity (p < 0.05) but no difference in basal loco-motion relative to control rats. There was no difference in acquisition of cocaine self-administration or infusions earned during the cocaine dose-response sessions between VTA 5-HT2C R knockdown and control rats. Conclusions: These data suggest reduced VTA 5-HT2C R tone confers an increased sensitivity to the hypermotive response but not the reinforcing properties of cocaine. Investigation into the role of VTA 5-HT2C R tone on other cocaine-related behaviors, such as motivation to respond for cocaine or cocaine cue reactivity, are underway and will provide further insight into which facets of responsivity to cocaine are modulated by 5-HT2C R function in the VTA. Financial support: DA035620, DA06511, DA024157, DA033935, DA033374. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.674
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Effects of intramuscular and oral buspirone on physiology and behavior in monkeys Kendall T. Szeliga, Susan E. Martelle, Michael A. Nader Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, United States Aims: Buspirone has multiple actions in the brain including dopamine (DA) D2-like receptor antagonism. Recent data suggest that buspirone has higher affinity at the DA D3 receptor (DAD3) compared to the DA D2 receptor (DAD2) subtype; DAD3 has been a target for medications to treat drug addiction. One behavioral assay that has been used to assess DAD3 and DAD2 involves administration of the D2-like agonist quinpirole (QUIN). QUIN elicits yawning and the ascending limb of the dose-response curve is thought to be DAD3 mediated, while higher doses of QUIN result in fewer yawns and in hypothermia; the latter is thought to be DAD2 mediated. The goal of this study was to examine, in separate groups of monkeys, the effects of buspirone administered by different routes on behavior (QUIN-elicited yawning) and physiology (QUIN-induced hypothermia). Methods: In drug-naïve male rhesus monkeys (n = 3), QUIN (0.01–0.3 mg/kg, i.m.) elicited yawning that was characterized as an inverted U-shaped function of dose, with peak yawning following 0.1 mg/kg QUIN. In a second study, drug-naïve female cynomolgus monkeys (n = 4) were surgically implanted with indwelling telemetry transmitters (D70-PCT; Data Sciences International, St. Paul, MN). QUIN (0.1 mg/kg, i.m.) induced significant hypothermia. Results: Irrespective of route, buspirone (0.1, i.m. and 0.3–1.0 mg/kg, p.o.) attenuated 0.1 mg/kg QUIN-elicited yawning. Intramuscular (0.1–0.56 mg/kg) but not oral (1.0–5.6 mg/kg) buspirone attenuated QUIN-induced hypothermia. Conclusions: The present data support the hypothesis that oral buspirone is primarily a DAD3 antagonist. If DAD3 is a viable target for addiction medications, then additional studies using oral buspirone are warranted. Financial support: DA012460 and DA010584. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.675 Lower oxidative stress in umbilical blood cord of newborns exposed to crack during pregnancy Claudia M. Szobot 1 , Maria Zavaschi 1 , V. Mardini 1 , F. Kapczinski 1 , Márcia Kauer-Sant’anna 1 , Gabriela Colpo 1 , Bianca Aguiar 1 , Gabrielle Cunha 1 , L. Manna 1 , Anna Rose Childress 2 , Daniel Langleben 2 , K.M. Cereser 1 , L.A. Rohde 1 1 Federal University of Rio Grande do Sul, Porto Alegre, Brazil 2 Treatment Research Center, Philadelphia, PA, United States
Aims: The use of crack-cocaine is a major health concern in several countries. Among its users, pregnant women and their newborns, exposed to crack-cocaine intrautero, deserve special attention. One of the toxic mechanisms of crack-cocaine consists of oxidative stress (OS), which plays an important role in the embryonic development, neonatal and pregnancy-related disorders. Little is known about OS in babies exposed to crack-cocaine during pregnancy. The aim of this study was to compare the levels of OS in newborns exposed to crack during pregnancy (EN) and nonexposed newborns (NEN).