- Email: [email protected]
P5.000 Alcohol-seeking and self-administration:Effects of a sono tonin 1B agonist in the nucleus accumbens
Ph. Addiction [4] Liu L, Ikonem S, Heikkin~m% etal., (2002). The effects of long-term trea~nemt with rnetrifonate, a oholinesterase inhibitor, on eholinergic activity, amyloid patholo~, and cognitive Nnotion in APP and PSI doubly transgenio mien. Exp. Neurol. 173(2) : 196-204.
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Prevention of brain ATP depletion after acute stress accounts for 15d-PGJ2 and rosiglitazone an ti-excitotoxic effect
B. Garcfa-Sueno, J.R. Case, M.R Pereira, J. Pradillo, I. Lizasoaln, M.A. More, R Lorenzo, J.C. Leza*. Dpt. of P~ar~aeology, Fee.
Medicine. Unia Comp~tense, Ma&id 2#040, @sin A growing body of evidence suggests that peroxisome proliferatoractivated receptor gamma (PPART) may play a role in inflammation since various PPARy ligands were shown to inhibit proinflammatory mediators. As it has been previously shown, immobilisation stress induces a rapid release of excitatory amino acids in various brain areas, which account for accumulation of oxidative/ nitrosative mediators in brain after the expression of enzymes such as iNOS and COX-2. On the other hand, some PPAR~' ligands such as 15d-PGJ2 (PGJ2) and rosiglitazone (RS) prevent stressinduced increase in iNOS/COX-2 related inflammatory events. To assess if this effect is related to the release of glutamate in brain after stress, Wiatar rats (control and immobilised during 6h, $6) received i.p. PGJ2 (120 Fg/kg) or RS (3 ms/ks) at the onset of immobilisation. Both PGJ2 and RS decrease stress-induced increase in plasma levels of glutamate (control: 9.24-0.9 pg/ml; $6: 132%, p<0.05 vs control; S6+PGJ2: 88%; S6+RS: 89%, both p<0.05 vs S6). Taken into account that a fall in ATP with the subsequent reversal of the glutamate uptake systems accounts for excitotoxic damage in brain, we tested this possibility. Interestingly, PGJ2 and RS revert the fall in brain ATP seen after stress (control: 0.0444-0.011 ~mol/mg prot; $6: 67.05%, p<0.05 vs control; Se+PGJ2:123.15%; Se+RS: 135.5%, both p<0.05 vs se). These findings suggest the possibility/of a pharmacological modulation for preventing accumulation of oxidative/nitrosative species and possble subsequent brain damage after stress exposure or in stress-related neuropsychological disorders.
PS. Addiction
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Alcohol-seeking and self-administration Effects ofa serotonin 1B agonist in the nucleus accumbens
C.L. Czachowski. Brown Unioers#y, Centerfor AlcoJ~ol and Addictio~ Studies, Providence, Jr~r, US.A. Alcohol, along with other behaviorally relevant stimuli, is bdieved to be processed through the neural circuit involving the ventral tegmental area (VTA), the nucleus accumbens (NAcc) and the prefrontal cortex (PFC). It is hypothesized that serotonin (5I-IT) affects ethanol-directed behaviors by interacting with the VTA/ PFC/NAcc system via projections from the dorsal raphe to the VTA and the NAoc. Two parallel experiments assessed the effects of a 5I-IT1B agonist (CGS12066B), microinjected directly into the NAcc, on reinforcer-seeking and consumption using the sipper tube appetitive/consummatory model of ethanol access. The 5KTlt) agonist binds presvnapfically to terminals, causing a decrease in serotonin out:put specifically to the NAcc in these experiments. Male Long Evans rats (n=8-11/group) were trained
$339
to complete a single response requirement (ZRZR)that resulted in access to 10% ethanol (Ethanol Groups) or 2% sucrose (Sucrose Groups) for a 20-rain drinking period. In the seeking experiment, reinforced sessions used a 20-1ever-press ZRZRand non-reinforced/ trea~nent sessions to assess the limit to the seeking response. The intake experiment utilized a lower RR (10 on non-treatment days, 1 on treatment days) to assure completion of the response and access to the sipper tube. In the seeking experiment, Ss were consuming an average of 0.7 g/ks ethanol and making approximately 50-80 responses during non-reinforced sham (no drug) sessions (Sucrose Group had similar baseline response levels). Microinjections of the 5HT1B agonist significantly reduced ethanol-seeking with no effect on sucrose-seeking. Moreover, start latencies and rates of responding indicated that there were no drug-induced changes in motor activity. In the intake experiment, drug treatment decreased ethanol intake and again, there was no treatment effect on sucrose intake. Overall, the manipulation of 51-IT activity in the NAcc specifically affected ethanol-reinforced responding with no effects on sucrose-reinforced responding, and seeking behaviors were more sensitive than drinking behaviors. Therefore, these findings suggest that a certain level of serotonin activity in the NAoc is necessary to generate ethanol-seeking, indicating a role for this system in alcohol "craving". Studies assessing the relative input of the VTA and both increases and decreases in serotonin activity throughout the dorsal raphe/VTA/NAoc circuit are ongoing.
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A
prospective study on the genetic and psychosocial effects on the change of alcohol drinking behavior of freshmen of a university
S.I. Lee j, H. Kim 2, I.W. Chung 1, C.J. Ghin 1, G.M. Hong a, Y.M. Kwon 1, K.H. Chi 4, K.Y. Lee 5, iCoEege of medicine,
C~ungbuk national un~oers~ Department of neuropsyc~at~ CJ~eonuu, Republic of Korea; :Col&go of meNcine, CJ~ungbuk national unioersiy, Department of preventive medicine, CheongN, RepubZie of Korea; SC~eonuu Saint Mary ~Hospita4 Department of Psy&~atrj4, Cl~eongju, ~Repub[~cof Korea; 4 Gongju national mental hosp#al, Department of pxyc/~Xatry, Go~gju, 2epublXc of Korea; Sgeoul national un~oerst~ ~osp#al, Department of psyc;~iatry, Seen4 RepuNic of Korea S~teillem o n tile p m ] ~ o s e : Alcohol drinking is a popular phenomenon in most society and It is known that alcohol drinking behavior in adolescence is maintained through adulthood, The fact that alcohol drinking rate of college students is higher than that of adults should be seriously considered, There have been many studies about psyohosocial factors associated with alcohol drinking behavior as well as candidate genes polymorphism associated with alcohol dependence, But, there is no comprehensive study about genetic and psyohosoical factors associated with alcohol drinking behavior and especially prospective follow-up study is needed, With this study, the authors want to achieve these objectives, 1, We investigate the distribution of NN, ND and DD type of Aldehyde Dehydrogenase (ALDH) ]I polymorphism and the differences of the characteristics and the changing pattern of alcohol behavior according to ALDK ]I polymorphism in freshmen, 2, We investigate the associations between the characteristics and the changing pattern of alcohol behavior and sociodemographic factors or psychological factors (motivation, expectancy and permission of alcohol drinking) and analyze the differences according to ALDH II polymorphism.
•
Prevention of brain ATP depletion after acute stress accounts for 15d-PGJ2 and rosiglitazone an ti-excitotoxic effect
B. Garcfa-Sueno, J.R. Case, M.R Pereira, J. Pradillo, I. Lizasoaln, M.A. More, R Lorenzo, J.C. Leza*. Dpt. of P~ar~aeology, Fee.
Medicine. Unia Comp~tense, Ma&id 2#040, @sin A growing body of evidence suggests that peroxisome proliferatoractivated receptor gamma (PPART) may play a role in inflammation since various PPARy ligands were shown to inhibit proinflammatory mediators. As it has been previously shown, immobilisation stress induces a rapid release of excitatory amino acids in various brain areas, which account for accumulation of oxidative/ nitrosative mediators in brain after the expression of enzymes such as iNOS and COX-2. On the other hand, some PPAR~' ligands such as 15d-PGJ2 (PGJ2) and rosiglitazone (RS) prevent stressinduced increase in iNOS/COX-2 related inflammatory events. To assess if this effect is related to the release of glutamate in brain after stress, Wiatar rats (control and immobilised during 6h, $6) received i.p. PGJ2 (120 Fg/kg) or RS (3 ms/ks) at the onset of immobilisation. Both PGJ2 and RS decrease stress-induced increase in plasma levels of glutamate (control: 9.24-0.9 pg/ml; $6: 132%, p<0.05 vs control; S6+PGJ2: 88%; S6+RS: 89%, both p<0.05 vs S6). Taken into account that a fall in ATP with the subsequent reversal of the glutamate uptake systems accounts for excitotoxic damage in brain, we tested this possibility. Interestingly, PGJ2 and RS revert the fall in brain ATP seen after stress (control: 0.0444-0.011 ~mol/mg prot; $6: 67.05%, p<0.05 vs control; Se+PGJ2:123.15%; Se+RS: 135.5%, both p<0.05 vs se). These findings suggest the possibility/of a pharmacological modulation for preventing accumulation of oxidative/nitrosative species and possble subsequent brain damage after stress exposure or in stress-related neuropsychological disorders.
PS. Addiction
•
Alcohol-seeking and self-administration Effects ofa serotonin 1B agonist in the nucleus accumbens
C.L. Czachowski. Brown Unioers#y, Centerfor AlcoJ~ol and Addictio~ Studies, Providence, Jr~r, US.A. Alcohol, along with other behaviorally relevant stimuli, is bdieved to be processed through the neural circuit involving the ventral tegmental area (VTA), the nucleus accumbens (NAcc) and the prefrontal cortex (PFC). It is hypothesized that serotonin (5I-IT) affects ethanol-directed behaviors by interacting with the VTA/ PFC/NAcc system via projections from the dorsal raphe to the VTA and the NAoc. Two parallel experiments assessed the effects of a 5I-IT1B agonist (CGS12066B), microinjected directly into the NAcc, on reinforcer-seeking and consumption using the sipper tube appetitive/consummatory model of ethanol access. The 5KTlt) agonist binds presvnapfically to terminals, causing a decrease in serotonin out:put specifically to the NAcc in these experiments. Male Long Evans rats (n=8-11/group) were trained
$339
to complete a single response requirement (ZRZR)that resulted in access to 10% ethanol (Ethanol Groups) or 2% sucrose (Sucrose Groups) for a 20-rain drinking period. In the seeking experiment, reinforced sessions used a 20-1ever-press ZRZRand non-reinforced/ trea~nent sessions to assess the limit to the seeking response. The intake experiment utilized a lower RR (10 on non-treatment days, 1 on treatment days) to assure completion of the response and access to the sipper tube. In the seeking experiment, Ss were consuming an average of 0.7 g/ks ethanol and making approximately 50-80 responses during non-reinforced sham (no drug) sessions (Sucrose Group had similar baseline response levels). Microinjections of the 5HT1B agonist significantly reduced ethanol-seeking with no effect on sucrose-seeking. Moreover, start latencies and rates of responding indicated that there were no drug-induced changes in motor activity. In the intake experiment, drug treatment decreased ethanol intake and again, there was no treatment effect on sucrose intake. Overall, the manipulation of 51-IT activity in the NAcc specifically affected ethanol-reinforced responding with no effects on sucrose-reinforced responding, and seeking behaviors were more sensitive than drinking behaviors. Therefore, these findings suggest that a certain level of serotonin activity in the NAoc is necessary to generate ethanol-seeking, indicating a role for this system in alcohol "craving". Studies assessing the relative input of the VTA and both increases and decreases in serotonin activity throughout the dorsal raphe/VTA/NAoc circuit are ongoing.
~
A
prospective study on the genetic and psychosocial effects on the change of alcohol drinking behavior of freshmen of a university
S.I. Lee j, H. Kim 2, I.W. Chung 1, C.J. Ghin 1, G.M. Hong a, Y.M. Kwon 1, K.H. Chi 4, K.Y. Lee 5, iCoEege of medicine,
C~ungbuk national un~oers~ Department of neuropsyc~at~ CJ~eonuu, Republic of Korea; :Col&go of meNcine, CJ~ungbuk national unioersiy, Department of preventive medicine, CheongN, RepubZie of Korea; SC~eonuu Saint Mary ~Hospita4 Department of Psy&~atrj4, Cl~eongju, ~Repub[~cof Korea; 4 Gongju national mental hosp#al, Department of pxyc/~Xatry, Go~gju, 2epublXc of Korea; Sgeoul national un~oerst~ ~osp#al, Department of psyc;~iatry, Seen4 RepuNic of Korea S~teillem o n tile p m ] ~ o s e : Alcohol drinking is a popular phenomenon in most society and It is known that alcohol drinking behavior in adolescence is maintained through adulthood, The fact that alcohol drinking rate of college students is higher than that of adults should be seriously considered, There have been many studies about psyohosocial factors associated with alcohol drinking behavior as well as candidate genes polymorphism associated with alcohol dependence, But, there is no comprehensive study about genetic and psyohosoical factors associated with alcohol drinking behavior and especially prospective follow-up study is needed, With this study, the authors want to achieve these objectives, 1, We investigate the distribution of NN, ND and DD type of Aldehyde Dehydrogenase (ALDH) ]I polymorphism and the differences of the characteristics and the changing pattern of alcohol behavior according to ALDK ]I polymorphism in freshmen, 2, We investigate the associations between the characteristics and the changing pattern of alcohol behavior and sociodemographic factors or psychological factors (motivation, expectancy and permission of alcohol drinking) and analyze the differences according to ALDH II polymorphism.