Cynthia Kuhn

Overview:

This laboratory uses a multidisciplinary approach using both animal and model systems to study the biology of addiction and stress/depression. We are specifically interested in how adolescence and the hormonal changes of puberty and aging influence vulnerability to these conditions. Specific projects underway include: (1) the biology of sex differences in addictive drug action, (2) role of maturing dopamine systems in the onset of drug taking during adolescence, (3) the neurobiology of adolescent insensitivity to threat and its role in drug use.
Studies of sex differences focus on understanding estrogen and testosterone actions in the brain that are relevant to addiction, depression and stress-related behaviors. We are particularly interested in molecular targets of estrogen action including key proteins that regulate dopamine neurons and the stress peptide CRF. Current projects include the role of glucocorticoid and reproductive hormones in alcohol and opioid dependence in adolescence.  Adolescent studies are exploring the impact of maturing dopamine systems as well as cortical inhibition of these systems on novelty-seeking/risk taking as predictors of substance abuse vulnerability as well as responses to addictive drugs.
In addition to these animal studies, we collaborate actively with clinicians in psychiatry who are studying addiction and stress-related illness in humans, and participate in development of drug-abuse education and general neuroscience education materials for students, parents and other members of the lay public.

Positions:

Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor in Psychiatry and Behavioral Sciences

Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences
School of Medicine

Faculty Network Member of the Duke Institute for Brain Sciences

Duke Institute for Brain Sciences
Institutes and Provost's Academic Units

Associate of the Duke Initiative for Science & Society

Duke Science & Society
Institutes and Provost's Academic Units

Affiliate of the Center for Child and Family Policy

Center for Child and Family Policy
Sanford School of Public Policy

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1976

Duke University

Grants:

Nasal adjuvant to enhance anti-cocaine vaccines

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Simultaneous and Bidirectional Chemogenetic Control of Mesolimbic and Nigrostriatal Circuits

Administered By
Basic Science Departments
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

PTSD & Childhood Sexual Abuse: Psychobiology

Administered By
Psychiatry, Child & Family Mental Health & Community Psychiatry
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

PTSD & Childhood Sexual Abuse: Psychobiology

Administered By
Psychiatry, Child & Family Mental Health & Community Psychiatry
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Child Neglect: Psychobiological Consequences

Administered By
Psychiatry, Child & Family Mental Health & Community Psychiatry
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Publications:

Correction to: Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

Authors
Reavis, ZW; Mirjankar, N; Sarangi, S; Boyle, SH; Kuhn, CM; Matson, WR; Babyak, MA; Matson, SA; Siegler, IC; Kaddurah-Daouk, R; Suarez, EC; Williams, RB; Grichnik, K; Stafford-Smith, M; Georgiades, A
MLA Citation
Reavis, Zackery W., et al. “Correction to: Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.Metabolomics, vol. 17, no. 6, June 2021, p. 56. Pubmed, doi:10.1007/s11306-021-01809-z.
URI
https://scholars.duke.edu/individual/pub1484459
PMID
34106337
Source
pubmed
Published In
Metabolomics
Volume
17
Published Date
Start Page
56
DOI
10.1007/s11306-021-01809-z

Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men). METHODS: CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015). RESULTS: Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences. CONCLUSION: Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.
Authors
Reavis, ZW; Mirjankar, N; Sarangi, S; Boyle, SH; Kuhn, CM; Matson, WR; Babyak, MA; Matson, SA; Siegler, IC; Kaddurah-Daouk, R; Suarez, EC; Williams, RB; Grichnik, K; Stafford-Smith, M; Georgiades, A
MLA Citation
Reavis, Zackery W., et al. “Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.Metabolomics, vol. 17, no. 2, Jan. 2021, p. 13. Pubmed, doi:10.1007/s11306-020-01757-0.
URI
https://scholars.duke.edu/individual/pub1472418
PMID
33462762
Source
pubmed
Published In
Metabolomics
Volume
17
Published Date
Start Page
13
DOI
10.1007/s11306-020-01757-0

The effects of peri-adolescent alcohol use on the developing hippocampus

Adolescence is a period of continued brain development. Regions of the brain, such as the hippocampus, continue to undergo refinement and maturation throughout adolescence and into early adulthood. Adolescence is also a time of heightened sensitivity to novelty and reward, which contribute to an increase in risk-taking behaviors including the use of drugs and alcohol. Importantly, binge drinking is highly prevalent among adolescents and emerging adults. The hippocampus which is important for the integration of emotion, reward, homeostasis, and memory is particularly vulnerable to the neurotoxic effects of alcohol. In this chapter, we cover the fundamentals of hippocampal neuroanatomy and the current state of knowledge of the acute and chronic effects of ethanol in adolescent humans and adolescent rodent models. We focus on the hippocampal-dependent behavioral, structural, and neurochemical changes and identify knowledge gaps in our understanding of age-dependent neurobiological effects of alcohol use.
Authors
Walker, CD; Kuhn, CM; Risher, ML
MLA Citation
Walker, C. D., et al. “The effects of peri-adolescent alcohol use on the developing hippocampus.” International Review of Neurobiology, 2021. Scopus, doi:10.1016/bs.irn.2021.08.003.
URI
https://scholars.duke.edu/individual/pub1496668
Source
scopus
Published Date
DOI
10.1016/bs.irn.2021.08.003

The role of sex in the persistent effects of adolescent alcohol exposure on behavior and neurobiology in rodents.

Alcohol drinking is often initiated during adolescence, and this frequently escalates to binge drinking. As adolescence is also a period of dynamic neurodevelopment, preclinical evidence has highlighted that some of the consequences of binge drinking can be long lasting with deficits persisting into adulthood in a variety of cognitive-behavioral tasks. However, while the majority of preclinical work to date has been performed in male rodents, the rapid increase in binge drinking in adolescent female humans has re-emphasized the importance of addressing alcohol effects in the context of sex as a biological variable. Here we review several of the consequences of adolescent ethanol exposure in light of sex as a critical biological variable. While some alcohol-induced outcomes, such as non-social approach/avoidance behavior and sleep disruption, are generally consistent across sex, others are variable across sex, such as alcohol drinking, sensitivity to ethanol, social anxiety-like behavior, and induction of proinflammatory markers.
Authors
Robinson, DL; Amodeo, LR; Chandler, LJ; Crews, FT; Ehlers, CL; Gómez-A, A; Healey, KL; Kuhn, CM; Macht, VA; Marshall, SA; Swartzwelder, HS; Varlinskaya, EI; Werner, DF
MLA Citation
Robinson, Donita L., et al. The role of sex in the persistent effects of adolescent alcohol exposure on behavior and neurobiology in rodents. Vol. 160, 2021, pp. 305–40. Pubmed, doi:10.1016/bs.irn.2021.07.007.
URI
https://scholars.duke.edu/individual/pub1494686
PMID
34696877
Source
pubmed
Volume
160
Published Date
Start Page
305
End Page
340
DOI
10.1016/bs.irn.2021.07.007

Correction to: 5-HTTLPR and Gender Moderate Changes in Negative Affect Responses to Tryptophan Infusion.

Authors
Brummett, BH; Muller, CL; Collins, AL; Boyle, SH; Kuhn, CM; Siegler, IC; Williams, RB; Suarez, EC; Ashley-Koch, A
MLA Citation
Brummett, Beverly H., et al. “Correction to: 5-HTTLPR and Gender Moderate Changes in Negative Affect Responses to Tryptophan Infusion.Behav Genet, vol. 51, no. 2, Mar. 2021, p. 163. Pubmed, doi:10.1007/s10519-020-10030-y.
URI
https://scholars.duke.edu/individual/pub1469069
PMID
33326061
Source
pubmed
Published In
Behav Genet
Volume
51
Published Date
Start Page
163
DOI
10.1007/s10519-020-10030-y