Getachew, Bruk

Hauser, Sheketha R

Taylor, Robert E

Tizabi, Yousef

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Washington University School of MedicineDigital Commons@BeckerPosters 2007: Alcohol Use Across the Lifespan2007Alcohol withdrawal results in depressive-likebehavior in ratsBruk GetachewHoward UniversitySheketha R. HauserHoward UniversityRobert E. TaylorHoward UniversityYousef TizabiHoward UniversityFollow this and additional works at: http://digitalcommons.wustl.edu/guzeposter2007Part of the Medicine and Health Sciences CommonsThis Poster is brought to you for free and open access by the 2007: Alcohol Use Across the Lifespan at Digital Commons@Becker. It has been acceptedfor inclusion in Posters by an authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationGetachew, Bruk; Hauser, Sheketha R.; Taylor, Robert E.; and Tizabi, Yousef, "Alcohol withdrawal results in depressive-like behavior inrats" (2007). Posters. Paper 1 Samuel B. Guze Symposium on Alcoholism.http://digitalcommons.wustl.edu/guzeposter2007/1ALCOHOL WITHDRAWAL RESULTS IN DEPRESSIVE-LIKE BEHAVIOR IN RATSBruk Getachew, Sheketha R. Hauser, Robert E. Taylor, Yousef TizabiHoward University, College of Medicine, Department of Pharmacology, Washington, DC 20059.INTRODUCTIONMany epidemiological studies report significant co-morbid expression of alcoholism and depression (Haver and Dahlgren, 1995). Ithas been suggested (Hasin & Grant, 2002; Kessler et al., 1997; Schuckit et al., 1997) that alcoholism may induce depression;however, a causal relationship between these two conditions is yet to be established.During alcohol withdrawal (AW) autonomic hyperactivity (De Witte, et al., 2003) and/or altered psychological states can facilitatethe relapse (Glenn and Parsons, 1991). In fact, depression appears to be particularly common during and following detoxification(Beck et al., 1993; Behar et al., 1984; Turnbull and Gomberg, 1988). Therefore, occurrence of depression during AW is animportant determinant of treatment seeking but worsens the prognosis in detoxifying alcoholics (Kendall and Clarkin 1992).Moreover, depression in alcoholics is underestimated diagnosed and undertreated.The major aim of this study was to determine whether withdrawal from chronic alcohol administration might lead to depressive-likebehavior in a rat model. Moreover, because of known strain-dependent responses to alcohol, the studies were carried out in twostrains of rats: the Wistar and Wistar-Kyoto (WKY). WKY rats, derived from the Wistar stock are considered an animal model ofdepression as they exhibit exaggerated immobility in the forced swim test (FST) compared to the Wistar rats.METHODSAnimalsAge matched adult female WKY and Wistar rats (Charles Rivers) were kept in a temperature-controlled room (24-26oC) on a 12:12 hour reversed light/dark cycle (lights on at 19:00). The animals had ad libitum access to food and water, except during experiments. Ethanol Vapor ExposureAnimals were exposed daily 95% ethanol via inhalation chamber (La Jolla Alcohol Research Inc. La Jolla, CA) for 7 or 14 days. Tominimize problems of ethanol vapor condensation, the following parameters were used: air pressure = 5 psi, airflow rate = 10-15 liter/min and alcohol flow rate = 10-75 ml/hr. Every 3 days blood Alcohol Level (BAL) was determined. Note: Mean BALs were equivalent in both groups during the alcohol exposure (approximately *150 mg/dl, at various time points). Behavioral TestingLocomotor Activity Test (LCA): On the day of behavioral testing i.e., day 8 and 15 (14-18 hr after last ethanol exposure) automated analysis of LCA in an open field was performed prior to the FST.Forced Swim TestA modification of the method of (Porsolt et al., 1977) was used. The FST measures immobility of animals in an inescapable cylinder of water. The total amount of time the animal demonstrates this behavior reflects the animal's state of behavioral despair. The animals were placed in the water cylinders for 5 minutes, videotaped and their swimming and immobility was scored at every 5 second internal according to Detke, et al., 1995. Statistical AnalysisAll data were expressed as the mean ± S.E.M. One-way analysis of variance (ANOVA) followed by Tukey’s post hoc test when significant main effects were indicated. All analyses were two-tailed and P<0.05 was considered significant.Figure 2A and B. Effects of 14-16 hour withdrawal from 2 weeks daily ethanolexposure on LCA and FST immobility of WKY and Wistar rats. Values are mean ± SEM.*P< 0.05. N=7-8.Summery of Results•WKY rats show lower baseline LCA compared to Wistar rats.•Withdrawal from 1 or 2 weeks daily ethanol resulted in significant LCA reduction in Wistar rats only.•Withdrawal from 1 or 2 weeks daily ethanol exposure resulted in increased FST immobility in both WKYs andWistars.Concluding StatementAlcohol Withdrawal may lead to depressive-like characteristics in at least two strains of rats. This model may be usedto investigate the neurobiological bases of affective disorder following alcohol withdrawal.ReferencesBeck, A.T. Wright, F. D. Newman, C. F and Liese B. S. Cognitive Therapy of Substance Abuse, The Guilford Press, New York (1993). Behar, D. Winokur,G. and Berg, C.J.  (1984) Depression in the abstinent alcoholic. Am. J. Psychiat. 144, 1105–1107.Detke, M. J., Rickels, M., Lucki, I. (1995) Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology (Berl).121, 66-72.De Witte, P. Pinto, E. Ansseau, M. Verbanck, P.  (2003) Alcohol and withdrawal: from animal research to clinical issues. Neurosci Biobehav Rev 27, 189-197. Glenn, S. W., & Parson, O. A. (1991) Impaired efficiency in female alcoholics’ neuropsychological performance. Journal of Clinical and Experimental Neuropsychology, 13(6), 895-908.Hasin, D. S. & Grant, B. F. (2002)Major Depression in 6050 Former Drinkers: Association With Past Dependence. Arch. Gen. Psychiatry 59, 794-800.Haver, B. & Dahlgren, L. (1995) Early treatment of women with alcohol addiction (EWA): a comprehensive evaluation and outcome study. I. Patterns of psychiatric co-morbidity at intake. Addiction, 90, 101-109.Kendall, P. C. and Clarkin, J. F. (1992) Journal of Consult Clinical  Psychol. 60, 833-4.Kessler, R. C.; Crum, R. M.; Warner, L. A.; et al. (1997) Lifetime co–occurence of DSM–III–R alcohol abuse and dependence with other psychiatric disorders in the National Co-morbidity Survey. Arch. of Gen. Psychiatry54, 313–321. Porsolt , R. D., Bertin, A. Jalfre M. (1977) Behavioral despair in mice:a primary screening test for antidepressants. Arch. Int Pharmacology Ther.  229: 327-36.Schuckit, M. A., Tipp, J. E., Bergman, M., Reich, W., Hesselbrock, V. M. and Smith, T. L. (1997) Comparison of induced and independent major depressive disorders in 2,945 alcoholics. American Journal of Psychiatry 154,   948–957. Turnbull, J.E. and Gomberg, E.S.L.(1988) Impact of depressive symptomatology on alcohol problems in women. Alcohol Clin. Exp. Res. 12, 374–381. RESULTSWeek 1WIS con WIS alcWKY conWKY alcAmbulatory Counts020040060080010001200WIS con WIS alcWKY conWKY alcImmobility (Counts)0102030405060A B***************LCA k 1 FST******Week 2WIS con WIS alcWKY conWKY alcAmbulatory Counts020040060080010001200WIS con WIS alcWKY conWKY alcImmobility (Counts)0102030405060*************A BLCA FST**eek 2******Results

Alcohol withdrawal results in depressive-like behavior in rats

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Alcohol withdrawal results in depressive-like behavior in rats

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