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; Sherman, Brian J; Brady, Kathleen T et al. (2018) Impact of endogenous progesterone on reactivity to yohimbine and cocaine cues in cocaine-dependent women. Pharmacol Biochem Behav 165:63-69 |
| Kohtz, Amy S; Lin, Belle; Smith, Michael E et al. (2018) Attenuated cocaine-seeking after oxytocin administration in male and female rats. Psychopharmacology (Berl) 235:2051-2063 |
| Moran-Santa Maria, Megan M; Vanderweyen, Davy C; Camp, Christopher C et al. (2018) Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study. Nicotine Tob Res 20:810-818 |
| Sherman, Brian J; Baker, Nathaniel L; Squeglia, Lindsay M et al. (2018) Approach bias modification for cannabis use disorder: A proof-of-principle study. J Subst Abuse Treat 87:16-22 |
| Tomko, Rachel L; Saladin, Michael E; Baker, Nathaniel L et al. (2018) Sex Differences in Subjective and Behavioral Responses to Stressful and Smoking Cues Presented in the Natural Environment of Smokers. Nicotine Tob Res : |
| Moreland, Angela D; McRae-Clark, Aimee (2018) Parenting outcomes of parenting interventions in integrated substance-use treatment programs: A systematic review. J Subst Abuse Treat 89:52-59 |
| Spencer, Sade; Neuhofer, Daniela; Chioma, Vivian C et al. (2018) A Model of ?9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens. Biol Psychiatry 84:601-610 |
| Cox, Brittney M; Bentzley, Brandon S; Regen-Tuero, Helaina et al. (2017) Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand. Biol Psychiatry 81:949-958 |
| Melis, Miriam; Frau, Roberto; Kalivas, Peter W et al. (2017) New vistas on cannabis use disorder. Neuropharmacology 124:62-72 |
| Leong, Kah-Chung; Freeman, Linnea R; Berini, Carole R et al. (2017) Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner. Int J Neuropsychopharmacol 20:844-854 |
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