The research in the Spencer lab is broadly aimed at identifying the neural mechanisms that underlie the initial development of drug addiction and the persistent vulnerability to relapse. We are also interested in gaining a better understanding of individual differences in vulnerability or treatment outcomes related to addiction. We currently study two primary research models: psychostimulants (cocaine) and cannabinoids (delta-9-tetrahydrocannibinol). There is currently no approved pharmacological treatment for the abuse of either of these drugs. We focus on glutamatergic plasticity in the mesocorticolimbic brain circuit because these brain regions exhibit dynamic neuroadaptations associated with different stages of chronic drug use and relapse that may offer important clues that can be leveraged to design more effective treatments for addictions. Our multidisciplinary approach includes quantitative analysis of gene and protein expression; genetic (optogenetic and chemogenetic), molecular, and pharmacological manipulations of neural circuits; measurement of neurochemical function using microdialysis and biosensors; and imaging of neuronal structure and activity with tools being optimized to move in vivo.
The lab website is: https://www.spencerlabatumn.com
- Neuhofer D, Spencer SM, Chioma VC, Beloate LN, Schwartz D, Kalivas PW. The loss of NMDAR-dependent LTD following cannabinoid self-administration is restored by positive allosteric modulation of CB1 receptors. Addict Biol. 2019 Nov 16:e12843.
- Namba MD, Kupchik YM, Spencer SM, Garcia-Keller C, Goenaga JG, Powell GL, Vicino IA, Hogue IB, Gipson CD. Accumbens neuroimmune signaling and dysregulation of astrocytic glutamate transport underlie conditioned nicotine-seeking behavior. Addict Biol. 2019 Jul 22:e12797. doi: 10.1111/adb.12797.
- Spencer S*, Neuhofer D*, Chioma V, Garcia-Keller C, Schwartz D, Allen N, Scofield M, Ortiz T, Kalivas PW. A model of Δ9‐tetrahydrocannabinol (THC) self-administration and reinstatement that produces heroin-like synaptic plasticity in nucleus accumbens. Biol Psychiatry. 2018;84:601-610.
- Spencer S, Garcia-Keller C, Roberts-Wolfe D, Heinsbroek JA, Mulvaney M, Sorrel A, Kalivas PW. Cocaine use reverses striatal plasticity produced during cocaine seeking. Biol Psychiatry. 2017;81(7):616- 624.
- Brown RM, Kupchik YM, Spencer S, Garcia-Keller C, Spanswick DC, Lawrence AJ, Simonds SE, Schwartz DJ, Jordan KA, Jhou TC, Kalivas PW. Addiction-like synaptic impairments in diet- induced obesity. Biol Psychiatry. 2017;81(9):797-806.
- Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR, Arey RN, Enwright JFIII, Jacobsen JPR, Kumar S, Remillard EM, Caron MG, Deisseroth K, McClung CA. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Mol Psychiatry. 2015; 20(11):1406-1419.
- Garcia-Keller, Kupchik YM, Gipson C, Brown RM, Spencer S, Bollati F, Roberts-Wolfe D, Heinsbroek JA, Cancela LM, Kalias PW. Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration. Mol Psychiatry. 2015;21(8):1063-1069.
- Spencer S, Brown RM, Quintero GC, Kupchik YM, Thomas C, Reissner KJ, Kalivas PW. Alpha2/delta-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse. J Neurosci. 2014;34(25):8605-8611.