Relapse is a persistent problem in cocaine addiction, and many important aspects ofthe brain mechanisms involved remain unknown. One key area for cocaine relapse in the rat model is the medial prefrontal cortex (mPFC);in particular, mPFC interactions with the nucleus accumbens (NA) and ventral tegmental area (VTA) are critical for reinstatement of extinguished cocaine seeking. Projects 1 and 2 in this center focus on molecular and cellular mechanisms involved in the mPFC-to-NA pathway during extinction and reinstatement. Little is known about the activities of neurons in mPFC that project to NA, or that receive dopamine (DA) from VTA, during these cocaine behaviors. Here, we will use Fos labeling and unit recording during extinction and reinstatement to measure impulse activity of mPFC neurons identified as projecting to NA core or shell. We also will capitalize on TH::Cre rats and optogenetics methods recently implemented in our lab to determine the influence of endogenous DA release on impulse activity of prelimbic cortex neurons that project to NA core during extinction and reinstatement. Together, these studies will provide an overall map of NA-projecting mPFC neurons that are activated during cocaine behaviors, and also measure their impulse activities with respect to specific task stimuli and behaviors during exinction or reinstatement of cocaine seeking. These findings will provide a detailed circuit analysis of behavior-related activities in these key mPFC neurons that will be important information to extend results of molecular- and cellular-level studies in other projects of this center.
Relapse to cocaine seeking is a long-lasting problem that remains clinically difficult to treat. The proposed studies will reveal changes in brain cortical neurons caused by cocaine abuse that promote relapse. These findings will integrate with other projects in this center to facilitate developing new treatments for cocaine addiction.
|Mulholland, Patrick J; Chandler, L Judson; Kalivas, Peter W (2016) Signals from the Fourth Dimension Regulate Drug Relapse. Trends Neurosci 39:472-85|
|Garcia-Keller, C; Kupchik, Y M; Gipson, C D et al. (2016) Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration. Mol Psychiatry 21:1063-9|
|Go, Bok Soon; Barry, Sarah M; McGinty, Jacqueline F (2016) Glutamatergic neurotransmission in the prefrontal cortex mediates the suppressive effect of intra-prelimbic cortical infusion of BDNF on cocaine-seeking. Eur Neuropsychopharmacol 26:1989-1999|
|Scofield, Michael D; Li, Hao; Siemsen, Benjamin M et al. (2016) Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core. Biol Psychiatry 80:207-15|
|Augur, Isabel F; Wyckoff, Andrew R; Aston-Jones, Gary et al. (2016) Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking. J Neurosci 36:10174-80|
|McGlinchey, Ellen M; James, Morgan H; Mahler, Stephen V et al. (2016) Prelimbic to Accumbens Core Pathway Is Recruited in a Dopamine-Dependent Manner to Drive Cued Reinstatement of Cocaine Seeking. J Neurosci 36:8700-11|
|Stefanik, Michael T; Kupchik, Yonatan M; Kalivas, Peter W (2016) Optogenetic inhibition of cortical afferents in the nucleus accumbens simultaneously prevents cue-induced transient synaptic potentiation and cocaine-seeking behavior. Brain Struct Funct 221:1681-9|
|Spencer, Sade; Garcia-Keller, Constanza; Roberts-Wolfe, Douglas et al. (2016) Cocaine Use Reverses Striatal Plasticity Produced During Cocaine Seeking. Biol Psychiatry :|
|Scofield, M D; Heinsbroek, J A; Gipson, C D et al. (2016) The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis. Pharmacol Rev 68:816-71|
|Back, Sudie E; McCauley, Jenna L; Korte, Kristina J et al. (2016) A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders. J Clin Psychiatry :|
Showing the most recent 10 out of 155 publications