Project I: Oxytocin and Cocaine Dependence Co-Principal Investigators: Kathleen Brady and Aimee McRae-Clark;Co-Investigators: Jane Joseph, Megan Moran-Santa Maria Response to stress may be important in understanding sex/gender differences in drug dependence and may also be a target for developing both psychotherapeutic and pharmacotherapeutic interventions. Our previous SCOR work has suggested that the HPA axis in women may be more sensitive to the toxic effects of cocaine or early life trauma as compared to men;furthermore, cocaine-dependent women have a greater physiologic and subjective response to stress and the magnitude of this response may be related to the potential for relapse. As such, therapies focused on modulation of the stress response might be particularly important for women. Oxytocin is a hypothalamic neuropeptide that has been shown to mediate behavioral responding to stress as well as play a role in neuroadaptations that occur as a consequence of long-term drug use. Given these effects, oxytocin may have a therapeutic role in ameliorating the negative affect commonly observed prior to relapse in cocaine-dependent individuals. As estrogen appears to enhance oxytocin's effects, women may have an enhanced response to oxytocin. We propose an evaluation of the impact of oxytocin on the endocrine, physiological and subjective response to a validated laboratory stressor (the Trier Social Stress Task) in cocaine-dependent men (n=76) and women (n=76). In addition, fMRI will be used to evaluate the impact of oxytocin on functional brain activity in limbic and striatal nuclei during a cue- reactivity task and to assess gender differences in the neural response to oxytocin. The impact of estrogen and progesterone on stress and cue reactivity will also be measured. To our knowledge, this will be the first clinical investigation of oxytocin in cocaine-dependent individuals. Consistent with the overall theme of the MUSC SCOR, this project will directly explore the mechanistic underpinnings of the stress response in cocaine dependent men and women, and provide important data on a potential treatment approach.
Stress is likely involved in relapse to cocaine use. This project will investigate the role oxytocin may play in the stress response in cocaine-dependent men and women and examine how oxytocin may impact brain activity in individuals exposed to cocaine-related cues.
|Moran-Santa Maria, Megan M; Hartwell, Karen J; Hanlon, Colleen A et al. (2015) Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers. Addict Biol 20:407-14|
|McClure, Erin A; Gipson, Cassandra D; Malcolm, Robert J et al. (2014) Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs 28:95-106|
|Bentzley, Brandon S; Jhou, Thomas C; Aston-Jones, Gary (2014) Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat. Proc Natl Acad Sci U S A 111:11822-7|
|Reichel, Carmela M; Gilstrap, Meghin G; Ramsey, Lauren A et al. (2014) Modafinil restores methamphetamine induced object-in-place memory deficits in rats independent of glutamate N-methyl-D-aspartate receptor expression. Drug Alcohol Depend 134:115-22|
|Cason, Angie M; Aston-Jones, Gary (2014) Role of orexin/hypocretin in conditioned sucrose-seeking in female rats. Neuropharmacology 86:97-102|
|Moran-Santa Maria, Megan M; Flanagan, Julianne; Brady, Kathleen (2014) Ovarian hormones and drug abuse. Curr Psychiatry Rep 16:511|
|McClure, Erin A; Acquavita, Shauna P; Dunn, Kelly E et al. (2014) Characterizing smoking, cessation services, and quit interest across outpatient substance abuse treatment modalities. J Subst Abuse Treat 46:194-201|
|Koch, F R; Wagner, C L; Jenkins, D D et al. (2014) Sex differences in cerebral blood flow following chorioamnionitis in healthy term infants. J Perinatol 34:197-202|
|Guille, C; Clark, S; Amstadter, A B et al. (2014) Trajectories of depressive symptoms in response to prolonged stress in medical interns. Acta Psychiatr Scand 129:109-15|
|Parsegian, Aram; See, Ronald E (2014) Dysregulation of dopamine and glutamate release in the prefrontal cortex and nucleus accumbens following methamphetamine self-administration and during reinstatement in rats. Neuropsychopharmacology 39:811-22|
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