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1996 March

cFos Induction in Response to Alcohol and Tastes Paired with Alcohol in Alcohol-Preferring (P) and Alcohol-Nonpreferring (NP) Rats

Ilene L. Bernstein, PhD


Description: Two selectively bred rat lines, developed to model genetic contributions to alcohol abuse, are alcohol preferring (P) and nonpreferring (NP) rats. As their name suggests, these lines differ significantly in their preference for alcohol and their willingness to ingest it. Although a number of biochemical differences between these two lines have been identified, a causal link between specific neurochemical differences and the behavior of interest remains speculative. Because initial taste reactions to ethanol do not differ, but experience with ethanol causes taste reactions of the lines to diverge, the present experiments focus on learning, that is, the role played by experience with alcohol and its postingestive effects, in determining alcohol intake and preference. The present study hypothesizes that the neural response to ethanol differs significantly in P and NP rats, and, as a consequence, the learned response to tastes paired with ethanol also comes to differ. We propose to use cFos immunohistochemistry, as a marker of neuronal activation, to identify line differences in the direct effects of ethanol, as well as the response to tastes previously paired with ethanol delivery. It is proposed that the differential acquisition of positive or negative reactions to the taste of ethanol ultimately drive injestive responses up or down, and are instrumental in generating strain differences.

Factors Related to the Prevention of Relapse and Recidivism in Incarcerated Women with a History of Drug Abuse

Dorothy J. Henderson, PhD, RN
Assistant Professor

Psychosocial and Community Health

Description: Substance abuse is one of the primary reasons for women to enter prison and is the primary health problem of women who are in prison. The purpose of this study is to develop and pilot an interview guide in order to more effectively gather relevant data from women felons pertaining to their potential for and protection from substance abuse relapse and criminal recidivism upon their release from prison. A combination of focus groups and ethnographic interviews will be conducted with incarcerated women with substance abuse disorders to gather information for the development and validation of the interview guide.

Effects of Chronic Ethanol Consumption on GABAergic Neurotransmission in the Neocortex

Johannes F.M. van Brederode, PhD
Research Assistant Professor


Description: Chronic ethanol consumption leads to the development of tolerance, physical dependence and withdrawal symptoms. Many studies have suggested that GABA, the major inhibitory neurotransmitter in the brain, plays a key role in these processes. The GABAergic system appears to 'adapt' to chronic ethanol consumption with a decrease in sensitivity to ethanol and allosteric modulators of GABA function. Several studies have suggested that the sub-unit composition of the GABAA receptor channel complex or the phosphorylation state of specific sub-units is responsible for functional changes in GABA function after chronic ethanol consumption. The purpose of this study is to determine if changes occur in the functional properties GABAA mediated neurotransmission in the neocortex, and if so, what the mechanisms are behind these changes. The study will use a rat model to mimic the alcohol dependence and withdrawal symptoms that are found in humans after consuming large amounts of alcohol for prolonged periods.

1996 October

Volumetric Reductions in Brain Regions Associated with Moderate Levels of in utero Alcohol Exposure

Susan J. Astley, PhD
Assistant Professor

Epidemiology, Pediatrics

Description: Fetal alcohol syndrome (FAS) is a permanent birth defect syndrome caused by maternal consumption of alcohol during pregnancy. FAS is characterized by growth deficiency, a unique cluster of minor facial anomalies and CNS dysfunction; however, many experience CNS dysfunction in the absence of other birth defects. Preliminary studies in humans with FAS have documented regional reductions in brain volume relative to normal controls. The question of whether or not volumetric reductions were detectable in fetal alcohol exposed individuals who present with cognitive/behavioral dysfunction in the absence of growth deficiency and facial anomalies will be explored. Cranial MR images of nonhuman primates exposed to ethanol in utero will be studied. Volumetric measurements will be made of selected brain regions to determine if reductions in size are associated with alcohol exposure and/or cognitive/behavioral outcomes in the absence of growth deficiency and full FAS facial anomalies.

Defining the Relationship between Sex and Drug Use

Donald A. Calsyn, PhD

Psychiatry & Behavioral Sciences

Description: A correlational link between sexual behavior and substance use has been identified. Opioids have an affect on sex hormone levels in humans; however, little is know about the relationship between these hormonal effects and the sexual behavior of opioid addicts. Interviews will be conducted with and blood specimens will be analyzed for sex related hormonal levels from opiate addicted clients. With the data obtained, the relationship between sexual behavior and hormonal levels will be explored.

Resulting articles & projects:

  • Data from this pilot project were used in NIDA CTN Protocol 0018, "Reducing HIV/STD Risk Behaviors: A Research Study for Men in Drug Abuse Treatment."
  • The project provided some pilot data related to a successful NIDA grant proposal "Computerized Assistance for Treatment Professionals in Assessment of Sexual Risk." 5R21DA022940-02
  • Calsyn DA, Wells EA, Saxon AJ, Heiman JR, Jackson R. Sexual desire and dysfunction among methadone maintenance clients. Drug Alcohol Depend 2001;63(S1):S23.
  • Calsyn DA, Wells EA, Saxon AJ, Jackson R, Heiman JR. Sexual activity under the influence of drugs is common among methadone clients. In Harris, L. (ed). Problems of Drug Dependence 1999, National Institute on Drug Abuse, NIH Pub. No. 00-4773, 315, 2000.
  • Calsyn DA, Wells EA, Saxon AJ, Jackson, R. Defining the relationship between sex and drugs. In Harris, L. (ed). Problems of Drug Dependence 1998, National Institute on Drug Abuse, NIH Pub. No. 99-4395, 268, 1999.

Placebo Controlled Examination of Valproate in the Treatment of Alcohol Withdrawal Syndrome

Joseph P. Reoux, MD
Acting Assistant Professor

Psychiatry & Behavioral Sciences

Description: Standard medical management of the alcohol withdrawal syndrome (AWS) routinely involves benzodiazepine medications. Benzodiazepines have some limitations, so a medication with advantages over benzodiazepine is desirable. Controlled studies have demonstrated the anticonvulsant carbamazepine to have equal efficacy in treating and a superior effect on psychological stress during AWS when compared to sedative hypnotics such as benzodiazepines. Although theoretical and mechanistic considerations indicate that another anticonvulsant, valproate, is likely to be effective as well, studies of valproate in AWS are much more limited, and placebo controlled, double blind examination of this treatment has not been performed. The proposed project tests the hypothesis that valproate is more effective than placebo in the management of the AWS in a double blind paradigm.

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