Contact
Biomedical Research Center251 Bayview Boulevard
Baltimore, MD 21224
Email: osama.abulseoud@nih.gov
Research Interests
Abulseoud is a staff scientist/ staff clinician. He received extensive post residency clinical and research training at the University of California Los Angeles, Magnetic Resonance Research Institute in California and the Mayo Clinic. His translational research focuses on discovering novel therapeutic interventions suitable for testing in clinical trials, and elucidating the role of glutamatergic signaling in the development of the comorbidity between addictive and mood disorders.
Publications
Selected Publications
2017 |
Gibson, William S; Cho, Shinho; Abulseoud, Osama A; Gorny, Krzysztof R; Felmlee, Joel P; Welker, Kirk M; Klassen, Bryan T; Min, Hoon-Ki; Lee, Kendall H The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity Journal Article Cerebral Cortex, 27 (3), pp. 2183-2194, 2017. @article{Gibson2017, title = {The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity}, author = {William S Gibson and Shinho Cho and Osama A Abulseoud and Krzysztof R Gorny and Joel P Felmlee and Kirk M Welker and Bryan T Klassen and Hoon-Ki Min and Kendall H Lee}, url = {https://academic.oup.com/cercor/article/27/3/2183/3056326}, doi = {10.1093/cercor/bhw074}, year = {2017}, date = {2017-01-01}, journal = {Cerebral Cortex}, volume = {27}, number = {3}, pages = {2183-2194}, abstract = {Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect. |
2016 |
Abulseoud, Osama A; Kasasbeh, Aimen; Min, Hoon-Ki; Fields, Julie A; Tye, Susannah J; Goerss, Stephan; Knight, Emily J; Sampson, Shirlene M; Klassen, Bryan T; Matsumoto, Joseph Y; Stoppel, Cynthia; Lee, Kendall H; Frye, Mark A Stereotact Funct Neurosurg, 94 (2), pp. 93–101, 2016, ISSN: 1423-0372 (Electronic); 1011-6125 (Linking). @article{Abulseoud2016, title = {Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates.}, author = {Osama A Abulseoud and Aimen Kasasbeh and Hoon-Ki Min and Julie A Fields and Susannah J Tye and Stephan Goerss and Emily J Knight and Shirlene M Sampson and Bryan T Klassen and Joseph Y Matsumoto and Cynthia Stoppel and Kendall H Lee and Mark A Frye}, url = {https://www.ncbi.nlm.nih.gov/pubmed/27093641}, doi = {10.1159/000445076}, issn = {1423-0372 (Electronic); 1011-6125 (Linking)}, year = {2016}, date = {2016-04-20}, journal = {Stereotact Funct Neurosurg}, volume = {94}, number = {2}, pages = {93--101}, address = {Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minn., USA.}, abstract = {BACKGROUND: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. METHODS: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. RESULTS: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. CONCLUSIONS: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. METHODS: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. RESULTS: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. CONCLUSIONS: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain. |
2015 |
Abulseoud, O A; Gawad, N A; Mohamed, K; Vadnie, C; Camsari, U M; Karpyak, V; Frye, M A; Choi, D-S Sex differences in mania phenotype and ethanol consumption in the lateral hypothalamic kindled rat model. Journal Article Transl Psychiatry, 5 , pp. e534, 2015, ISSN: 2158-3188 (Electronic); 2158-3188 (Linking). @article{Abulseoud2015, title = {Sex differences in mania phenotype and ethanol consumption in the lateral hypothalamic kindled rat model.}, author = {O A Abulseoud and N A Gawad and K Mohamed and C Vadnie and U M Camsari and V Karpyak and M A Frye and D-S Choi}, url = {https://www.ncbi.nlm.nih.gov/pubmed/25803497}, doi = {10.1038/tp.2015.30}, issn = {2158-3188 (Electronic); 2158-3188 (Linking)}, year = {2015}, date = {2015-03-24}, journal = {Transl Psychiatry}, volume = {5}, pages = {e534}, address = {Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.}, abstract = {Sex differences have been observed in mania phenotypes in humans. However the mechanisms underlying this difference are poorly understood. Activating the lateral hypothalamus is implicated in manic-like behaviors in rodents. Using newly established lateral hypothalamus kindled (LHK) rat mania model, we investigated sex differences of manic-like behaviors and its correlation with voluntary ethanol intake. We stimulated the lateral hypothalamus bilaterally in the male and female Wistar rats over five consecutive days. We recorded and quantified kindling-induced behaviors for each individual animal. We also assessed ethanol consumption using a two-bottle choice ethanol drinking as well as circadian locomotor activity counts daily throughout the experiment. We found notable sex differences in several aspects of manic-like behaviors during kindling. Males exhibited a significantly increased locomotor activity during the light phase, and reduced rest interval. On the other hand, females displayed significantly higher ethanol consumption and more frequent rearing behavior. However, no sex differences were present in the duration of sexual, feeding or grooming behaviors or in dark-phase activity counts. The excessive alcohol intake in LHK female rats is reminiscent of clinically reported sex differences in bipolar patients while the other phenotypic sex differences such as rearing and locomotor activity are less clearly described in clinical studies. Overall, our results lend further evidence for the validity of the LHK rat as a useful model to study brain region-specific molecular changes during mania and its correlation with alcohol use disorders.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sex differences have been observed in mania phenotypes in humans. However the mechanisms underlying this difference are poorly understood. Activating the lateral hypothalamus is implicated in manic-like behaviors in rodents. Using newly established lateral hypothalamus kindled (LHK) rat mania model, we investigated sex differences of manic-like behaviors and its correlation with voluntary ethanol intake. We stimulated the lateral hypothalamus bilaterally in the male and female Wistar rats over five consecutive days. We recorded and quantified kindling-induced behaviors for each individual animal. We also assessed ethanol consumption using a two-bottle choice ethanol drinking as well as circadian locomotor activity counts daily throughout the experiment. We found notable sex differences in several aspects of manic-like behaviors during kindling. Males exhibited a significantly increased locomotor activity during the light phase, and reduced rest interval. On the other hand, females displayed significantly higher ethanol consumption and more frequent rearing behavior. However, no sex differences were present in the duration of sexual, feeding or grooming behaviors or in dark-phase activity counts. The excessive alcohol intake in LHK female rats is reminiscent of clinically reported sex differences in bipolar patients while the other phenotypic sex differences such as rearing and locomotor activity are less clearly described in clinical studies. Overall, our results lend further evidence for the validity of the LHK rat as a useful model to study brain region-specific molecular changes during mania and its correlation with alcohol use disorders. |
Hitschfeld, Mario J; Schneekloth, Terry D; Ebbert, Jon O; Hall-Flavin, Daniel K; Karpyak, Victor M; Abulseoud, Osama A; Patten, Christi A; Geske, Jennifer R; Frye, Mark A Female smokers have the highest alcohol craving in a residential alcoholism treatment cohort. Journal Article Drug Alcohol Depend, 150 , pp. 179–182, 2015, ISSN: 1879-0046 (Electronic); 0376-8716 (Linking). @article{Hitschfeld2015, title = {Female smokers have the highest alcohol craving in a residential alcoholism treatment cohort.}, author = {Mario J Hitschfeld and Terry D Schneekloth and Jon O Ebbert and Daniel K Hall-Flavin and Victor M Karpyak and Osama A Abulseoud and Christi A Patten and Jennifer R Geske and Mark A Frye}, url = {https://www.ncbi.nlm.nih.gov/pubmed/25746235}, doi = {10.1016/j.drugalcdep.2015.02.016}, issn = {1879-0046 (Electronic); 0376-8716 (Linking)}, year = {2015}, date = {2015-02-25}, journal = {Drug Alcohol Depend}, volume = {150}, pages = {179--182}, address = {Department of Psychiatry & Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN, USA; Mental Health Service, Sotero Del Rio Hospital, Avenida Concha y Toro 3459, Puente Alto, Santiago, Chile.}, abstract = {BACKGROUND: Cigarette smoking among female and male alcoholics has not been extensively studied as a factor related to intensity of alcohol craving during residential treatment and corresponding sobriety length. METHODS: This retrospective cohort study assessed self-reported sobriety outcomes in patients with alcohol dependence at 3-month intervals over 12 months after completion of a 30-day residential treatment program. Demographic and clinical variables were collected including smoking status, alcohol craving utilizing the Penn Alcohol Craving Scale (PACS), and alcohol relapse. Statistical analyses included Chi-square, ANOVA, Tukey's test, Kaplan-Meier plots and Cox proportional hazards models as appropriate. RESULTS: Of the 761 alcohol-dependent study subjects, 355 (47%) were current smokers. Alcohol craving intensity was higher in smoking females compared to nonsmoking females (p=0.0096), smoking males (p<0.0001), and nonsmoking males (p<0.0001). Smoking status-by-sex interaction was not associated with post-treatment relapse. After controlling for other variables, higher PACS scores at admission were associated with higher probability of relapse (p=0.0003). CONCLUSIONS: In this study, female alcoholic smokers experienced the highest level of alcohol craving in an alcohol treatment setting. Interestingly, this did not translate into higher rates of post-treatment relapse. Further research is warranted to explore the neurobiological basis for sex differences in this highly prevalent comorbidity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Cigarette smoking among female and male alcoholics has not been extensively studied as a factor related to intensity of alcohol craving during residential treatment and corresponding sobriety length. METHODS: This retrospective cohort study assessed self-reported sobriety outcomes in patients with alcohol dependence at 3-month intervals over 12 months after completion of a 30-day residential treatment program. Demographic and clinical variables were collected including smoking status, alcohol craving utilizing the Penn Alcohol Craving Scale (PACS), and alcohol relapse. Statistical analyses included Chi-square, ANOVA, Tukey's test, Kaplan-Meier plots and Cox proportional hazards models as appropriate. RESULTS: Of the 761 alcohol-dependent study subjects, 355 (47%) were current smokers. Alcohol craving intensity was higher in smoking females compared to nonsmoking females (p=0.0096), smoking males (p<0.0001), and nonsmoking males (p<0.0001). Smoking status-by-sex interaction was not associated with post-treatment relapse. After controlling for other variables, higher PACS scores at admission were associated with higher probability of relapse (p=0.0003). CONCLUSIONS: In this study, female alcoholic smokers experienced the highest level of alcohol craving in an alcohol treatment setting. Interestingly, this did not translate into higher rates of post-treatment relapse. Further research is warranted to explore the neurobiological basis for sex differences in this highly prevalent comorbidity. |
2014 |
Cuellar-Barboza, Alfredo B; Frye, Mark A; Grothe, Karen; Prieto, Miguel L; Schneekloth, Terry D; Loukianova, Larissa L; Hall-Flavin, Daniel K; Clark, Matthew M; Karpyak, Victor M; Miller, Joseph D; Abulseoud, Osama A Change in consumption patterns for treatment-seeking patients with alcohol use disorder post-bariatric surgery. Journal Article J Psychosom Res, 78 (3), pp. 199–204, 2014, ISSN: 1879-1360 (Electronic); 0022-3999 (Linking). @article{Cuellar-Barboza2014, title = {Change in consumption patterns for treatment-seeking patients with alcohol use disorder post-bariatric surgery.}, author = {Alfredo B Cuellar-Barboza and Mark A Frye and Karen Grothe and Miguel L Prieto and Terry D Schneekloth and Larissa L Loukianova and Daniel K Hall-Flavin and Matthew M Clark and Victor M Karpyak and Joseph D Miller and Osama A Abulseoud}, url = {https://www.ncbi.nlm.nih.gov/pubmed/25258356}, doi = {10.1016/j.jpsychores.2014.06.019}, issn = {1879-1360 (Electronic); 0022-3999 (Linking)}, year = {2014}, date = {2014-09-07}, journal = {J Psychosom Res}, volume = {78}, number = {3}, pages = {199--204}, address = {Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States; Department of Psychiatry, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.}, abstract = {OBJECTIVE: The aim of this study is to describe the clinical phenotype of alcohol use disorder (AUD) treatment-seeking patients with Roux-en-Y Gastric Bypass Surgery (RYGB) history; and to compare it to AUD obese non-RYGB controls. METHODS: Retrospective study of electronic medical records for all patients 30-60years treated at the Mayo Clinic Addiction Treatment Program, between June, 2004 and July, 2012. Comparisons were performed with consumption patterns pre-RYGB and at time of treatment; excluding patients with AUD treatments pre-RYGB. RESULTS: Forty-one out of 823 patients had a RYGB history (4.9%); 122 controls were selected. Compared to controls, the RYGB group had significantly more females [n=29 (70.7%) vs. n=35 (28.7%) p<0.0001]; and met AUD criteria at a significantly earlier age (19.1+/-0.4 vs. 25.0+/-1years old}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVE: The aim of this study is to describe the clinical phenotype of alcohol use disorder (AUD) treatment-seeking patients with Roux-en-Y Gastric Bypass Surgery (RYGB) history; and to compare it to AUD obese non-RYGB controls. METHODS: Retrospective study of electronic medical records for all patients 30-60years treated at the Mayo Clinic Addiction Treatment Program, between June, 2004 and July, 2012. Comparisons were performed with consumption patterns pre-RYGB and at time of treatment; excluding patients with AUD treatments pre-RYGB. RESULTS: Forty-one out of 823 patients had a RYGB history (4.9%); 122 controls were selected. Compared to controls, the RYGB group had significantly more females [n=29 (70.7%) vs. n=35 (28.7%) p<0.0001]; and met AUD criteria at a significantly earlier age (19.1+/-0.4 vs. 25.0+/-1years old |
Abulseoud, Osama A; Camsari, Ulas M; Ruby, Christina L; Mohamed, Khalid; Gawad, Noha Abdel M; Kasasbeh, Aimen; Yuksel, Mehmet Y; Choi, Doo-Sup Lateral hypothalamic kindling induces manic-like behavior in rats: a novel animal model. Journal Article Int J Bipolar Disord, 2 (1), pp. 7, 2014, ISSN: 2194-7511 (Print); 2194-7511 (Linking). @article{Abulseoud2014b, title = {Lateral hypothalamic kindling induces manic-like behavior in rats: a novel animal model.}, author = {Osama A Abulseoud and Ulas M Camsari and Christina L Ruby and Khalid Mohamed and Noha M Abdel Gawad and Aimen Kasasbeh and Mehmet Y Yuksel and Doo-Sup Choi}, url = {https://www.ncbi.nlm.nih.gov/pubmed/26092394}, doi = {10.1186/s40345-014-0007-8}, issn = {2194-7511 (Print); 2194-7511 (Linking)}, year = {2014}, date = {2014-06-14}, journal = {Int J Bipolar Disord}, volume = {2}, number = {1}, pages = {7}, address = {Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA, Abulseoud.Osama@mayo.edu.}, abstract = {The lateral hypothalamus integrates critical physiological functions such as the sleep-wake cycle, energy expenditure, and sexual behaviors. These functions are severely dysregulated during mania. In this study, we successfully induced manic-like behavioral phenotypes in adult, male Wistar rats through bilateral lateral hypothalamic area kindling (LHK). To test the validity of the model, we studied the effect of standard antimanic medications lithium (47.5 mg/kg) or valproic acid (200 mg/kg) twice/day for 15 days in attenuating manic-like behaviors in the LHK rat. Compared with pre-kindling behaviors, LHK rats displayed significantly increased sexual self-stimulation (P = 0.034), excessive rearing (P = 0.0005), feeding (P = 0.013), and grooming (P = 0.007) during the kindling interval. LHK rats also drank more alcohol during the mania-induction days compared with baseline ethanol consumption levels (P = 0.01). Moreover, LHK rat exhibited increased total locomotor activity (P = 0.02) with reduced rest interval (P < 0.001) during the mania induction and post-mania days compared with baseline activity levels and rest intervals. Chronic administration of lithium or valproic acid significantly attenuated manic-like behaviors in the LHK rat model. Given the behavioral phenotype and the response to standard antimanic medications, the LHK rats may provide a model for studying manic psychopathology in humans.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The lateral hypothalamus integrates critical physiological functions such as the sleep-wake cycle, energy expenditure, and sexual behaviors. These functions are severely dysregulated during mania. In this study, we successfully induced manic-like behavioral phenotypes in adult, male Wistar rats through bilateral lateral hypothalamic area kindling (LHK). To test the validity of the model, we studied the effect of standard antimanic medications lithium (47.5 mg/kg) or valproic acid (200 mg/kg) twice/day for 15 days in attenuating manic-like behaviors in the LHK rat. Compared with pre-kindling behaviors, LHK rats displayed significantly increased sexual self-stimulation (P = 0.034), excessive rearing (P = 0.0005), feeding (P = 0.013), and grooming (P = 0.007) during the kindling interval. LHK rats also drank more alcohol during the mania-induction days compared with baseline ethanol consumption levels (P = 0.01). Moreover, LHK rat exhibited increased total locomotor activity (P = 0.02) with reduced rest interval (P < 0.001) during the mania induction and post-mania days compared with baseline activity levels and rest intervals. Chronic administration of lithium or valproic acid significantly attenuated manic-like behaviors in the LHK rat model. Given the behavioral phenotype and the response to standard antimanic medications, the LHK rats may provide a model for studying manic psychopathology in humans. |
Abulseoud, Osama A; Camsari, Ulas M; Ruby, Christina L; Kasasbeh, Aimen; Choi, Sun; Choi, Doo-Sup Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2. Journal Article Neuropsychopharmacology, 39 (7), pp. 1674–1684, 2014, ISSN: 1740-634X (Electronic); 0893-133X (Linking). @article{Abulseoud2014, title = {Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2.}, author = {Osama A Abulseoud and Ulas M Camsari and Christina L Ruby and Aimen Kasasbeh and Sun Choi and Doo-Sup Choi}, url = {https://www.ncbi.nlm.nih.gov/pubmed/24452391}, doi = {10.1038/npp.2014.14}, issn = {1740-634X (Electronic); 0893-133X (Linking)}, year = {2014}, date = {2014-01-23}, journal = {Neuropsychopharmacology}, volume = {39}, number = {7}, pages = {1674--1684}, address = {Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA.}, abstract = {Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a beta-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3-5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a beta-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3-5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS. |
2013 |
Sailasuta, Napapon; Harris, Kent C; Tran, Thao T; Abulseoud, Osama; Ross, Brian D Impact of fasting on human brain acid-base homeostasis using natural abundance (13) C and (31) P MRS. Journal Article J Magn Reson Imaging, 39 (2), pp. 398–401, 2013, ISSN: 1522-2586 (Electronic); 1053-1807 (Linking). @article{Sailasuta2013, title = {Impact of fasting on human brain acid-base homeostasis using natural abundance (13) C and (31) P MRS.}, author = {Napapon Sailasuta and Kent C Harris and Thao T Tran and Osama Abulseoud and Brian D Ross}, url = {https://www.ncbi.nlm.nih.gov/pubmed/23733582}, doi = {10.1002/jmri.24166}, issn = {1522-2586 (Electronic); 1053-1807 (Linking)}, year = {2013}, date = {2013-06-03}, journal = {J Magn Reson Imaging}, volume = {39}, number = {2}, pages = {398--401}, address = {Huntington Medical Research Institutes, Pasadena, California, USA.}, abstract = {PURPOSE: To use (13) C magnetic resonance spectroscopy (MRS) and (31) P MRS to develop a direct assay for regional [HCO3-] in the human brain and to define brain pH and physiological response of [HCO3-] to fasting. MATERIALS AND METHODS: Seven healthy subjects underwent MRS examinations on a 1.5T MRI scanner. Subjects were well fed with repeated examinations performed after 4 and 12 hours of fasting. Proton noise decoupling (13) C MRS were acquired using pulse and acquired acquisition while (31) P MRS were acquired using a 2D chemical shift imaging method with relaxation time (TR) of 2 seconds. RESULTS: Fasting brain bicarbonate concentrations (6.7 +/- 2.5 mM for 12-hour fasting}, keywords = {}, pubstate = {published}, tppubtype = {article} } PURPOSE: To use (13) C magnetic resonance spectroscopy (MRS) and (31) P MRS to develop a direct assay for regional [HCO3-] in the human brain and to define brain pH and physiological response of [HCO3-] to fasting. MATERIALS AND METHODS: Seven healthy subjects underwent MRS examinations on a 1.5T MRI scanner. Subjects were well fed with repeated examinations performed after 4 and 12 hours of fasting. Proton noise decoupling (13) C MRS were acquired using pulse and acquired acquisition while (31) P MRS were acquired using a 2D chemical shift imaging method with relaxation time (TR) of 2 seconds. RESULTS: Fasting brain bicarbonate concentrations (6.7 +/- 2.5 mM for 12-hour fasting |
2012 |
Abulseoud, Osama A; Miller, Joseph D; Wu, Jinhua; Choi, Doo-Sup; Holschneider, Daniel P Brain Research, 1456 , pp. 14 - 21, 2012, ISSN: 0006-8993. @article{ABULSEOUD201214, title = {Ceftriaxone upregulates the glutamate transporter in medial prefrontal cortex and blocks reinstatement of methamphetamine seeking in a condition place preference paradigm}, author = {Osama A Abulseoud and Joseph D Miller and Jinhua Wu and Doo-Sup Choi and Daniel P Holschneider}, url = {http://www.sciencedirect.com/science/article/pii/S0006899312005793}, doi = {https://doi.org/10.1016/j.brainres.2012.03.045}, issn = {0006-8993}, year = {2012}, date = {2012-01-01}, journal = {Brain Research}, volume = {1456}, pages = {14 - 21}, abstract = {Glutamate signaling plays an essential role in drug-seeking behavior. Using reinstatement of conditioned place preference (CPP), we determined whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of the glutamate transporter (EAAT2) on glial cells, blocks methamphetamine-triggered reinstatement of CPP. Rats acquired methamphetamine CPP following 7 consecutive days of conditioning, during which each animal received pairings of alternating morning methamphetamine (2.5mg/kg, IP) and afternoon saline (IP). Animals showing CPP were successfully extinguished with repeated twice daily saline administration over a 7-day period. Ceftriaxone (200mg/kg, IP) was administered (vs. saline) once a day for 7days during the extinction period. Upon successful extinction, animals received a single dose of methamphetamine (2.5mg/kg, IP) for reinstatement and were tested for CPP one day later. Using real time PCR, EAAT2 mRNA levels in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were quantified in response to ceftriaxone. Ceftriaxone blocked methamphetamine-triggered reinstatement of CPP and significantly increased EAAT2 mRNA levels in the mPFC, with a trend towards significance in the NAc. In conclusion, Ceftriaxone modulated the expression of the glutamate transporter in a critical region of the cortico-striatal addiction circuitry and attenuated drug-seeking behavior in rats. Further research is needed to test the efficacy of compounds targeting the EAAT2 in human methamphetamine-dependent users.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Glutamate signaling plays an essential role in drug-seeking behavior. Using reinstatement of conditioned place preference (CPP), we determined whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of the glutamate transporter (EAAT2) on glial cells, blocks methamphetamine-triggered reinstatement of CPP. Rats acquired methamphetamine CPP following 7 consecutive days of conditioning, during which each animal received pairings of alternating morning methamphetamine (2.5mg/kg, IP) and afternoon saline (IP). Animals showing CPP were successfully extinguished with repeated twice daily saline administration over a 7-day period. Ceftriaxone (200mg/kg, IP) was administered (vs. saline) once a day for 7days during the extinction period. Upon successful extinction, animals received a single dose of methamphetamine (2.5mg/kg, IP) for reinstatement and were tested for CPP one day later. Using real time PCR, EAAT2 mRNA levels in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were quantified in response to ceftriaxone. Ceftriaxone blocked methamphetamine-triggered reinstatement of CPP and significantly increased EAAT2 mRNA levels in the mPFC, with a trend towards significance in the NAc. In conclusion, Ceftriaxone modulated the expression of the glutamate transporter in a critical region of the cortico-striatal addiction circuitry and attenuated drug-seeking behavior in rats. Further research is needed to test the efficacy of compounds targeting the EAAT2 in human methamphetamine-dependent users. |
2009 |
Sailasuta, Napapon; Abulseoud, Osama; Harris, Kent C; Ross, Brian D Glial dysfunction in abstinent methamphetamine abusers. Journal Article J Cereb Blood Flow Metab, 30 (5), pp. 950–960, 2009, ISSN: 1559-7016 (Electronic); 0271-678X (Linking). @article{Sailasuta2009, title = {Glial dysfunction in abstinent methamphetamine abusers.}, author = {Napapon Sailasuta and Osama Abulseoud and Kent C Harris and Brian D Ross}, url = {https://www.ncbi.nlm.nih.gov/pubmed/20040926}, doi = {10.1038/jcbfm.2009.261}, issn = {1559-7016 (Electronic); 0271-678X (Linking)}, year = {2009}, date = {2009-12-30}, journal = {J Cereb Blood Flow Metab}, volume = {30}, number = {5}, pages = {950--960}, address = {Clinical Spectroscopy Unit, Huntington Medical Research Institutes, Pasadena, California 91105, USA. sailasuta@hmri.org}, abstract = {Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized (13)C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial (13)C-bicarbonate production rate from [1-(13)C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 micromol/g per min (N=5) versus controls 0.11 micromol/g per min (N=5)}, keywords = {}, pubstate = {published}, tppubtype = {article} } Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized (13)C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial (13)C-bicarbonate production rate from [1-(13)C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 micromol/g per min (N=5) versus controls 0.11 micromol/g per min (N=5) |
