The IRCSSA will investigate mechanisms underlying stress, self-control and addictive behaviors. Thedevelopment of addictive, or compulsive behaviors, is hypothesized to involve a combination of loss ofinhibitory (self) control over behavior and enhanced motivation for rewards. A wealth of data has shownprofound effects of stress on virtually all aspects of addictive behavior and our data suggest that chronicstress can facilitate the development of habitual or compulsive responses. We hypothesize that stresspromotes the transition from goal-directed to habitual behavioral patterns through effects governed by bothstriatal and prefrontal cortical (RFC) brain structures. The expression of addictive behavior is alsoassociated with increases in the motivational impact of reward-associated cues, effects thought to bemediated by the nucleus accumbens (NAc) a critical site for the motivational aspects of both natural anddrug rewards. Both the RFC and the NAc receive afferent dopaminergic input from the ventral tegmentalarea (VTA), and the RFC receives and noradrenergic inputs from the locus coeruleus (LC), and theseprojections are activated both by stress and addictive drugs. Stress also increases levels of corticotrophinreleasing-factor (CRF), a neuropeptide with an important role in integrating responses to stress. Since boththe VTA and LC express CRF receptors, stress-induced increases in CRF in these regions may provide alink by which stress can influence the cognitive-motivational processes underlying addictive behavior.
Aim 1 will test the hypothesis that chronic stress produces cognitive deficits and motivational alterations associatedwith compulsive behavior in experimental animals by concurrently reducing inhibitory control and enhancingthe motivational impact of reward-associated cues, thereby promoting the development of instrumentalhabits.
Aim 2 will use selective RNAi-based approaches to determine the role of VTA and LC CRF receptorsin the effects of stress on these food-motivated behaviors.
Aim 3 will explore stress-induced changes in geneexpression in the LC and VTA. Together, these studies will complement the imaging studies on stressinducedalterations in cortico-limbic-striatal function and behavioral/cellular studies on endocannabinoids andcatecholaminergic signaling in RFC pyramidal neurons and PFC-striatal circuits, as well as projects on cueinducedcraving and self-control/decision making in human and animal models. Findings from these studieswill elucidate brain mechanisms underlying stress induced compulsive behaviors that can then lead to newdrug development and therapies for preventing and decreasing compulsive behaviors such as addictions.
| Gourley, Shannon L; Olevska, Anastasia; Gordon, Jessica et al. (2013) Cytoskeletal determinants of stimulus-response habits. J Neurosci 33:11811-6 |
| Olausson, Peter; Kiraly, Drew D; Gourley, Shannon L et al. (2013) Persistent effects of prior chronic exposure to corticosterone on reward-related learning and motivation in rodents. Psychopharmacology (Berl) 225:569-77 |
| Gourley, Shannon L; Olevska, Anastasia; Zimmermann, Kelsey S et al. (2013) The orbitofrontal cortex regulates outcome-based decision-making via the lateral striatum. Eur J Neurosci 38:2382-8 |
| Quinn, Jennifer J; Pittenger, Christopher; Lee, Anni S et al. (2013) Striatum-dependent habits are insensitive to both increases and decreases in reinforcer value in mice. Eur J Neurosci 37:1012-21 |
| Gourley, Shannon L; Swanson, Andrew M; Koleske, Anthony J (2013) Corticosteroid-induced neural remodeling predicts behavioral vulnerability and resilience. J Neurosci 33:3107-12 |
| Barker, Jacqueline M; Zhang, Yuqi; Wang, Fan et al. (2013) Ethanol-induced Htr3a promoter methylation changes in mouse blood and brain. Alcohol Clin Exp Res 37 Suppl 1:E101-7 |
| Torregrossa, Mary M; Xie, Maylene; Taylor, Jane R (2012) Chronic corticosterone exposure during adolescence reduces impulsive action but increases impulsive choice and sensitivity to yohimbine in male Sprague-Dawley rats. Neuropsychopharmacology 37:1656-70 |
| Guarnieri, Douglas J; Brayton, Catherine E; Richards, Sarah M et al. (2012) Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction. Biol Psychiatry 71:358-65 |
| Gourley, Shannon L; Espitia, Jonathan W; Sanacora, Gerard et al. (2012) Antidepressant-like properties of oral riluzole and utility of incentive disengagement models of depression in mice. Psychopharmacology (Berl) 219:805-14 |
| Narayanan, Nandakumar S; Land, Benjamin B; Solder, John E et al. (2012) Prefrontal D1 dopamine signaling is required for temporal control. Proc Natl Acad Sci U S A 109:20726-31 |
Showing the most recent 10 out of 29 publications
