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publications

Featured Publications:

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Cocaine use reverses striatal plasticity produced during cocaine seeking

Relapse is a two-component process consisting of a highly motivated drug-seeking phase that, if successful, is followed by a drug-using phase resulting in temporary satiation. In rodents, cue-induce drug seeking requires transient synaptic potentiation (t-SP) of cortical glutamatergic synapses on nucleus accumbens core medium spiny neurons, but it is unknown how achieving drug use affects this plasticity. We modeled the two phases of relapse after extinction from cocaine self-administration to assess how cocaine use affects t-SP associated with cue-induced drug seeking.

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A Model of Δ9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens.

Photo credit: Rachel Poli.

In our manuscript, we describe a model of intravenous delta9-tetrahydrocannabinol plus cannabidiol self-administration and reinstatement in the rat. We show that this self-administration is CB1 receptor dependent as it can be blocked by rimonabant. We report that cue-induced reinstatement is inhibited by administration of drugs that have been shown to reduce relapse to other drugs of abuse (n-acetylcysteine, nNOS inhibitor, and matrix metalloproteinase 9 inhibitor). Finally, we report that THC self-administration and extinction results in enduring changes in structural and functional plasticity in the nucleus accumbens.

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The nucleus accumbens: mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis

This is a comprehensive review of the role that glutamate signal transduction in the nucleus accembens plays in addiction-related behaviors. As a major input structure of the basal ganglia, the nucleus accumbens integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to drugs of abuse disrupts plasticity in this region producing adaptations that serve as the molecular basis for relapse vulnerability, allowing drug-associated cues to engender a pathologic motivation for drug seeking.

Recent Peer-Reviewed Publications

  1. Brewer, A. L., Felter, C. E., Sternitzky, A. R., & Spencer, S. M. (2024). Somatic and anxiety-like behaviors in male and female rats during withdrawal from the non-selective cannabinoid agonist WIN 55,212–2. Pharmacology, Biochemistry and Behavior, 236, 173707-. https://doi.org/10.1016/j.pbb.2024.173707

  2. Aruldas, R., Orenstein, L. B., & Spencer, S. (2023). Metformin Prevents Cocaine Sensitization: Involvement of Adenosine Monophosphate-Activated Protein Kinase Trafficking between Subcellular Compartments in the Corticostriatal Reward Circuit. International Journal of Molecular Sciences, 24(23), 16859-. https://doi.org/10.3390/ijms242316859

  3. Chan A, Willard A, Mulloy S, Ibrahim N, Sciaccotta A, Schonfeld M, Spencer SM. (2022) Metformin in nucleus accumbens core reduce cue-induced cocaine seeking in male and female rats. Addiction Biology. 27(3):e13165. doi: 10.1111/adb.13165 PMID: 35470560

  4. Turk MC, Bakker CJ, Spencer SM, Lofgren SM. (2022) Systematic review of sex differences in the relationship between hormones and depression in HIV. Psychoneuroendocrinology. 138:105665. doi:10.1016/j.psyneuen.2022.105665. PMID: 35063687.

  5. Spencer S, Burrows C, Lacher SE, Macheledt KC, Berge JM, Ghebre RG. (2021) Framework for advancing equity in academic medicine and science: Perspectives from early career female faculty during the COVID-19 pandemic. Preventive Medicine Reports. 24:101576. doi:10.1016/j.pmedr.2021.101576. PMID: 34692377.

  6. Rinehart L and Spencer S. (2021) Which came first: Cannabis use or deficits in impulse control? Progress in Neuropsychopharmacology and Biological Psychiatry. 106:110066. doi:10.1016/j.pnpbp.2020.110066. PMID: 32795592.

  7. Neuhofer D, Spencer SM, Chioma VC, Beloate LN, Schwartz D, Kalivas PW. (2020) The loss of NMDAR-dependent LTD following cannabinoid self-administration is restored by positive allosteric modulation of CB1 receptors. Addiction Biology. 25(6):e12843. doi: 10.1111/adb.12843. PMID: 31733097.

  8. Garcia-Keller C, Neuhofer D, Bobadilla AC, Spencer S, Chioma VC, Monforton C, Kalivas PW. Extracellular Matrix Signaling Through β3 Integrin Mediates Cocaine Cue-Induced Transient Synaptic Plasticity and Relapse. (2019) Biological Psychiatry. 86(5):377-387. doi: 10.1016/biopsych.2019.03.982. PMID: 31126696.

  9. Spencer S*, Neuhofer D*, Chioma V, Garcia-Keller C, Schwartz D, Allen N, Scofield M, Ortiz T, Kalivas PW. (2018) A model of Δ9‐tetrahydrocannabinol (THC) self-administration and reinstatement that alters synaptic plasticity in nucleus accumbens. Biological Psychiatry. 84(8):601-610. PMID: 29861097. PMCID: PMC6162175.

  10. Spencer S and Kalivas PW. (2017) Glutamate transport: a new bench to bedside mechanism for treating substance abuse. International Journal of Neuropsychopharmacology. 20(10):797-812. PMID: 28605494. PMCID: 5632313.

  11. Spencer S, Garcia-Keller C, Roberts-Wolfe D, Heinsbroek JA, Mulvaney M, Sorrel A, Kalivas PW. (2017) Cocaine use reverses striatal plasticity produced during cocaine seeking. Biological Psychiatry. 81(7):616-624.  PMID: 27837917. PMCID: 5346331.

    >Featuredin“Early Career Investigator Commentary”article: Ferguson, D. (2017) Cocaine mediates the Cellular Mechanisms of Satiation. Biological Psychiatry. 81(7):e47-e48.

  12. Spencer S, Brown RM, Quintero GC, Kupchik YM, Thomas C, Reissner KJ, Kalivas PW. (2014) Alpha2delta-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse. Journal of Neuroscience. 34(25):8605-8611. PMID: 24948814. PMCID: 4061396.

>Featured in“Research Highlights”article: Bucci M. (2014) Your channels on Drugs. Nature Chemical Biology. 10(8):607.