P.6.a.003 Oxytocin potently antagonises behavioural and neuronal ethanol effects: involvement of...
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S654 P.6.a. Addiction − Alcohol (basic) The statistically significant increase of DNA damages in the placenta (in 3.7 times) and in the fetal tissues (in 3 times) also was revealed in 3 hours after alcohol administration in the group of low-sensitivity to alcohol animals. It should be noted that the DNA damages level in the animals after a 6-hour alcohol exposure is 31% higher than in animals after 3 hours of exposure. We have shown that the anxiolytic and antiteratogen Afobazole is able to reduce ethanol-induced DNA-damages in embryonic and placental tissues of rats exposed to ethanol. This drug reduces the negative effects of alcohol in behavioral reactions in pups of rats. The DNA damage were shown to correlate with disorder of the behavioral reactions of rats exposed to alcohol. Conclusions: Thus, the ability of ethanol to induce primary DNA damages in cells of placentas and rat embryos was demon- strated. In therapeutic doses Afobazole reduces the genotoxic ef- fect of ethanol. The protective effect of Afobazole more expressed in the cells of the embryo. Afobazole reduces the disorders of the behavioral reactions induced by DNA damage in pups of rats exposed to alcohol. P.6.a.003 Oxytocin potently antagonises behavioural and neuronal ethanol effects: involvement of GABA A d subunit-containing receptors S.T. Peters 1° , M.T. Bowen 2 , N. Absalom 3 , M. Chebib 3 , I.S. McGregor 2 , I.D. Neumann 1 1 University of Regensburg, Behavioural and Molecular Neurobiology, Regensburg, Germany; 2 University of Sydney, School of Psychology, Sydney, Australia; 3 University of Sydney, Faculty of Pharmacy, Sydney, Australia The consumption of alcoholic beverages is a common feature of social gatherings and a burden of modern societies. Therefore, alcohol (EtOH) is one of the most frequent drugs of abuse world- wide with the majority of the Western and modern cultures regu- larly consuming EtOH mainly due to its stress-reducing and mood exhilarating effects. Consuming EtOH at high doses and for a long time period results in socioeconomic as well as health problems including organ damage, immune dysfunctions and cognitive im- pairments. However, despite a continuously increasing knowledge and substantial research interest, the etiology of EtOH abuse and binge intoxication remains poorly elucidated with only a few treat- ment options available [1]. In this context, brain neuropeptides, such as oxytocin (OXT), have emerged as promising treatment options for abuse disorders. Preclinical studies revealed that OXT is involved in reward and addiction-related behaviours [2]. Here, we first revealed that an acute intracerebroventricular (icv) infusion of OXT (1 mg/5 ml) attenuated the voluntary EtOH (20%) self-administration after chronic intermittent access to EtOH for 45 days in male Wistar rats compared to vehicle (VEH)-treated animals. Next, we tested whether the OXT effect on EtOH intake is accompanied by an alteration of the EtOH-induced dopamine release within the Nucleus accumbens (NAc). An acute intraperi- toneal (ip) injection of EtOH (1.5 g/kg) increased the dopamine release within the NAc both in EtOH naive male Wistar rats as well as after 10 daily ip injections of EtOH. Icv OXT (1 mg/5 ml) completely blocked this EtOH-induced dopamine release in EtOH- naive and chronically treated rats compared to VEH-treated an- imals, which may explain the reduced EtOH self-administration following icv OXT. Next, we assessed whether icv OXT (1 mg/5 ml) affects motoric dysfunctions (ataxia) five and 10 min after an acute ip administration of EtOH. Specifically, OXT diminished the EtOH-induced motoric impairments as revealed by the loss of righting reflex and in the wire-hang tests, and by general locomo- tor activity in the open field and in the home cage. As preclinical studies indicate the d-subunit containing GABA A receptors to mediate the effects of EtOH, we finally performed electrophys- iological studies (two electrode voltage clamp) on xenopus laevis oocytes to test whether OXT is able to inhibit EtOH activity at d- subunit containing constructs. Synthetic OXT (10mM) reduced the EtOH-induced (30mM; the circulating concentration following ip EtOH at 1.5 g/kg [3]) increase in GABA-stimulated (3nM, 30nM) activity at d-subunit containing constructs. These effects of OXT at cellular level were peptide-specific, as the structurally related neuropeptide arginine vasopressin did not affect the EtOH-induced potentiation in GABAergic activity. These electrophysiological data provide a possible cellular mechanism for the effects of OXT on EtOH consumption, and EtOH-induced dopamine release within the NAc and ataxia. In summary, our results provide important insights into the potential role of OXT modulating and attenuating EtOH-induced behavioural and neuronal effects. Further studies are required to substantiate OXT as a possible medication for treating alcoholism. References [1] Spanagel, R., Alcoholism: a systems approach from molecular physi- ology to addictive behavior. Physiol Rev, 2009. 89(2): p. 649–705. [2] Carson, D.S., et al., A brief history of oxytocin and its role in modulating psychostimulant effects. J Psychopharmacol, 2013. 27(3): p. 231−47. [3] Walker, B.M. and C.L. Ehlers, Age-related differences in the blood alcohol levels of Wistar rats. Pharmacol Biochem Behav, 2009. 91(4): p. 560−5. P.6.a.004 Gender differences of alcohol dependence in Russia and in Germany M. Denisenko 1° 1 Nizhniy Novgorod Mental Health Clinic Nr. 1, Department of Health, Nizhniy Novgorod, Russia Objective: Globalization made transcultural researches very im- portant. Distinctions in psychosocial factors of alcohol depen- dence in different cultures may not allow using strategies of treatment from one country in another. During this study alcohol- dependent men and women from Russia and Germany were examined to find out, whether there were any differences in so- ciodemographical variables, drinking history, alcoholization style, complication and treatment results among alcohol-dependent pa- tients hospitalized for treating withdrawal syndrome. Material and Methods: 75 patients (48 men and 27 women) from Department of addictive behavior, University Hospital Essen, Germany and 100 patient (50 men and 50 women) from State Clinic of addictive behavior, Nizhny Novgorod, Russian, who fulfilled ICD-10 criteria for alcohol dependence were interviewed using SCID (Structured Clinical Interview for DSM-IV), CIWA (Clinical Institute Withdrawal Assessment for Alcohol), EuropASI (European Addiction Severity Index). For data collection about drug therapy, accompanying somatic disorders and results of hospitalization were used medical records. Results: Russian and German women do not differ in respect of age, educational level and marital status. There were 38% women from Russia with full-time job (p = 0.03) while among German women there were 30% with part time job (p = 0.003). There were significant more Russian men who were married (30%, p = 0.0007) whereas among German men there were more
Transcript of P.6.a.003 Oxytocin potently antagonises behavioural and neuronal ethanol effects: involvement of...
S654 P.6.a. Addiction − Alcohol (basic)
The statistically significant increase of DNA damages in theplacenta (in 3.7 times) and in the fetal tissues (in 3 times) alsowas revealed in 3 hours after alcohol administration in the groupof low-sensitivity to alcohol animals. It should be noted that theDNA damages level in the animals after a 6-hour alcohol exposureis 31% higher than in animals after 3 hours of exposure. We haveshown that the anxiolytic and antiteratogen Afobazole is able toreduce ethanol-induced DNA-damages in embryonic and placentaltissues of rats exposed to ethanol. This drug reduces the negativeeffects of alcohol in behavioral reactions in pups of rats. The DNAdamage were shown to correlate with disorder of the behavioralreactions of rats exposed to alcohol.
Conclusions: Thus, the ability of ethanol to induce primaryDNA damages in cells of placentas and rat embryos was demon-strated. In therapeutic doses Afobazole reduces the genotoxic ef-fect of ethanol. The protective effect of Afobazole more expressedin the cells of the embryo. Afobazole reduces the disorders of thebehavioral reactions induced by DNA damage in pups of ratsexposed to alcohol.
P.6.a.003 Oxytocin potently antagonises behavioural
and neuronal ethanol effects: involvement of
GABAA d subunit-containing receptors
S.T. Peters1 °, M.T. Bowen2, N. Absalom3, M. Chebib3,I.S. McGregor2, I.D. Neumann1 1University of Regensburg,Behavioural and Molecular Neurobiology, Regensburg, Germany;2University of Sydney, School of Psychology, Sydney, Australia;3University of Sydney, Faculty of Pharmacy, Sydney, Australia
The consumption of alcoholic beverages is a common feature ofsocial gatherings and a burden of modern societies. Therefore,alcohol (EtOH) is one of the most frequent drugs of abuse world-wide with the majority of the Western and modern cultures regu-larly consuming EtOH mainly due to its stress-reducing and moodexhilarating effects. Consuming EtOH at high doses and for a longtime period results in socioeconomic as well as health problemsincluding organ damage, immune dysfunctions and cognitive im-pairments. However, despite a continuously increasing knowledgeand substantial research interest, the etiology of EtOH abuse andbinge intoxication remains poorly elucidated with only a few treat-ment options available [1]. In this context, brain neuropeptides,such as oxytocin (OXT), have emerged as promising treatmentoptions for abuse disorders. Preclinical studies revealed that OXTis involved in reward and addiction-related behaviours [2].Here, we first revealed that an acute intracerebroventricular (icv)
infusion of OXT (1 mg/5ml) attenuated the voluntary EtOH (20%)self-administration after chronic intermittent access to EtOH for45 days in male Wistar rats compared to vehicle (VEH)-treatedanimals. Next, we tested whether the OXT effect on EtOH intakeis accompanied by an alteration of the EtOH-induced dopaminerelease within the Nucleus accumbens (NAc). An acute intraperi-toneal (ip) injection of EtOH (1.5 g/kg) increased the dopaminerelease within the NAc both in EtOH naive male Wistar rats aswell as after 10 daily ip injections of EtOH. Icv OXT (1mg/5ml)completely blocked this EtOH-induced dopamine release in EtOH-naive and chronically treated rats compared to VEH-treated an-imals, which may explain the reduced EtOH self-administrationfollowing icv OXT. Next, we assessed whether icv OXT (1 mg/5ml)affects motoric dysfunctions (ataxia) five and 10min after anacute ip administration of EtOH. Specifically, OXT diminished
the EtOH-induced motoric impairments as revealed by the loss ofrighting reflex and in the wire-hang tests, and by general locomo-tor activity in the open field and in the home cage. As preclinicalstudies indicate the d-subunit containing GABAA receptors tomediate the effects of EtOH, we finally performed electrophys-iological studies (two electrode voltage clamp) on xenopus laevisoocytes to test whether OXT is able to inhibit EtOH activity at d-subunit containing constructs. Synthetic OXT (10mM) reduced theEtOH-induced (30mM; the circulating concentration following ipEtOH at 1.5 g/kg [3]) increase in GABA-stimulated (3nM, 30nM)activity at d-subunit containing constructs. These effects of OXTat cellular level were peptide-specific, as the structurally relatedneuropeptide arginine vasopressin did not affect the EtOH-inducedpotentiation in GABAergic activity.These electrophysiological data provide a possible cellular
mechanism for the effects of OXT on EtOH consumption, andEtOH-induced dopamine release within the NAc and ataxia.In summary, our results provide important insights into the
potential role of OXT modulating and attenuating EtOH-inducedbehavioural and neuronal effects. Further studies are required tosubstantiate OXT as a possible medication for treating alcoholism.
References
[1] Spanagel, R., Alcoholism: a systems approach from molecular physi-ology to addictive behavior. Physiol Rev, 2009. 89(2): p. 649–705.
[2] Carson, D.S., et al., A brief history of oxytocin and its role inmodulating psychostimulant effects. J Psychopharmacol, 2013. 27(3):p. 231−47.
[3] Walker, B.M. and C.L. Ehlers, Age-related differences in the bloodalcohol levels of Wistar rats. Pharmacol Biochem Behav, 2009. 91(4):p. 560−5.
P.6.a.004 Gender differences of alcohol dependence in
Russia and in Germany
M. Denisenko1 ° 1Nizhniy Novgorod Mental Health Clinic Nr.1, Department of Health, Nizhniy Novgorod, Russia
Objective: Globalization made transcultural researches very im-portant. Distinctions in psychosocial factors of alcohol depen-dence in different cultures may not allow using strategies oftreatment from one country in another. During this study alcohol-dependent men and women from Russia and Germany wereexamined to find out, whether there were any differences in so-ciodemographical variables, drinking history, alcoholization style,complication and treatment results among alcohol-dependent pa-tients hospitalized for treating withdrawal syndrome.
Material and Methods: 75 patients (48 men and 27 women)from Department of addictive behavior, University Hospital Essen,Germany and 100 patient (50 men and 50 women) from StateClinic of addictive behavior, Nizhny Novgorod, Russian, whofulfilled ICD-10 criteria for alcohol dependence were interviewedusing SCID (Structured Clinical Interview for DSM-IV), CIWA(Clinical Institute Withdrawal Assessment for Alcohol), EuropASI(European Addiction Severity Index). For data collection aboutdrug therapy, accompanying somatic disorders and results ofhospitalization were used medical records.
Results: Russian and German women do not differ in respectof age, educational level and marital status. There were 38%women from Russia with full-time job (p = 0.03) while amongGerman women there were 30% with part time job (p = 0.003).There were significant more Russian men who were married(30%, p = 0.0007) whereas among German men there were more
