High rates of relapse characterize drug and food addiction. Relapse is often preceded by subjective reports of intense craving and these cravings can be induced by drug or food-paired stimuli. Rats will press a lever for the presentation of a stimulus complex (a tone + light) previously associated with their food or drug taking, providing a model of cue-induced craving. We have demonstrated (Nature, 412:141-2, 2001) that responding for a stimulus previously associated with cocaine intake increases over the course of forced abstinence from self-administration (13-fold increase by 60 days of forced abstinence). We labeled the phenomenon an """"""""incubation of craving"""""""" and have observed the effect in rats following sucrose self- administration. In recent studies, we have found that inactivation of the nucleus accumbens, a brain region involved in motivated behavior, attenuates the incubation of craving for either cocaine or sucrose. The experiments outlined in this proposal will further explore the role of the nucleus accumbens in the incubation of craving effect in sucrose-experienced animals. Dopamine and glutamate are known to functionally interact in the nucleus accumbens and have been linked to relapse behaviors. Core and shell subregion distinctions have also been made in this regard. Specifically, we propose to attempt to block the incubation of craving by challenging accumbal core and shell subregions with antagonists of dopamine and glutamate receptors at Day 1 or Day 30 of forced abstinence. All experiments in this proposal are designed to allow full participation of undergraduate and master's level students in an area of research usually reserved for Ph.D. students and post-doctoral researchers. These experiments will further our understanding of the incubation of craving effect and will influence the direction of future grant proposals from our laboratory. Information gained from this project may also provide direction for behavioral therapy and medications-based therapy for drug addiction and eating disorders. Relapse characterizes drug and food addictions. These are major public health problems. The studies in this proposal aim to identify neural substrates of relapse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
3R15DA016285-02S2
Application #
7847030
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Lynch, Minda
Project Start
2003-04-01
Project End
2010-10-31
Budget Start
2009-06-01
Budget End
2010-10-31
Support Year
2
Fiscal Year
2009
Total Cost
$39,862
Indirect Cost
Name
Western Washington University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
079253134
City
Bellingham
State
WA
Country
United States
Zip Code
98225
Grimm, Jeffrey W; Glueck, Edwin; Ginder, Darren et al. (2018) Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats. Sci Rep 8:13174
Glueck, Edwin; Ginder, Darren; Hyde, Jeff et al. (2017) Effects of dopamine D1 and D2 receptor agonists on environmental enrichment attenuated sucrose cue reactivity in rats. Psychopharmacology (Berl) 234:815-825
Slaker, Megan; Barnes, Jesse; Sorg, Barbara A et al. (2016) Impact of Environmental Enrichment on Perineuronal Nets in the Prefrontal Cortex following Early and Late Abstinence from Sucrose Self-Administration in Rats. PLoS One 11:e0168256
Harkness, John H; Wells, Jason; Webb, Sierra et al. (2016) Extended exposure to environmental cues, but not to sucrose, reduces sucrose cue reactivity in rats. Learn Behav 44:59-66
Aoyama, Kenjiro; Barnes, Jesse; Koerber, Jon et al. (2016) Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats. Appetite 105:8-13
Grimm, Jeffrey W; Barnes, Jesse L; Koerber, Jonathon et al. (2016) Effects of acute or chronic environmental enrichment on regional Fos protein expression following sucrose cue-reactivity testing in rats. Brain Struct Funct 221:2817-30
Aoyama, K; Barnes, J; Grimm, J W (2014) Incubation of saccharin craving and within-session changes in responding for a cue previously associated with saccharin. Appetite 72:114-22
Grimm, Jeffrey W; Weber, Rachel; Barnes, Jesse et al. (2013) Brief exposure to novel or enriched environments reduces sucrose cue-reactivity and consumption in rats after 1 or 30 days of forced abstinence from self-administration. PLoS One 8:e54164
Koerber, Jonathon; Goodman, David; Barnes, Jesse L et al. (2013) The dopamine D2 antagonist eticlopride accelerates extinction and delays reacquisition of food self-administration in rats. Behav Pharmacol 24:633-9
Grimm, Jeffrey W; Ratliff, Christine; North, Kindsey et al. (2012) Nicotine increases sucrose self-administration and seeking in rats. Addict Biol 17:623-33

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