The current proposal compares adolescent and adult rats, both before and after cocaine self-administration, to appraise whether inherent or drug-induced changes in dopamine cell activity could underlie adolescent addiction liability. Recovery Act funds are being requested to expand the scope of the current project by adding stress as a possible factor that could influence adolescent addiction liability. Stress plays a critical role in drug addiction and may enhance addiction liability via its effects on dopamine transmission. It is unknown whether adolescents and adults are differentially sensitive to these effects of stress, or if drug exposure during adolescence vs. adulthood differentially modifies subsequent reactivity to stress. These are important questions because age-related differences in stress- and drug-induced neuroadaptations could underlie differences between adolescents and adults in susceptibility to drug self-administration and relapse.
Specific aims to address these questions are: to determine if adolescent and adult rats are differentially sensitive to stress-induced increases in drug intake and dopamine cell activity (Aim 1), and to determine if rats are more susceptible to stress-induced relapse and increases in dopamine cell activity if they experienced drugs during adolescence vs. adulthood (Aim 2).
Both aims answer important and independent questions about the interaction between stress and drug associated behaviors, and the potential role of dopamine cells in these effects. Importantly, they will help us understand if the effects of stress are influenced by the age at which the stress is experienced or if they are influenced by the age at which the drug is experienced. This revision will accelerate progress towards the important goal of understanding how stress could impact adolescent addiction liability. This is an important topic that that fits into NIDA's goal to solicit research that integrates environmental and developmental variables in order to have a better understanding of drug addiction. This revision also fits into the objectives of the Recovery Act, as it will stimulate the economy by enabling the hiring and retention of staff. Specifically, funds will be used to support a new student and to retain an excellent Research Technician whose position would otherwise be terminated fall 2009, given that she was hired on startup funds that are ending summer/fall 2009. In addition, this revision is also expected to stimulate the economy by enabling the purchase of new components for our operant self-administration cages, which are necessary to perform the experiments proposed in this application.

Public Health Relevance

These studies examine the role of stress and dopamine in adolescent addiction liability. They use a novel combination of well-established techniques in animal models to provide a better understanding of the etiology of adolescent addiction. In the long run, these studies will offer new insights into the development of treatment strategies that could prevent the development of addiction and relapse to drug taking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA020654-04S1
Application #
7814892
Study Section
Special Emphasis Panel (ZRG1-IFCN-L (95))
Program Officer
Volman, Susan
Project Start
2009-09-30
Project End
2011-09-29
Budget Start
2009-09-30
Budget End
2011-09-29
Support Year
4
Fiscal Year
2009
Total Cost
$385,000
Indirect Cost
Name
Rosalind Franklin University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
069501252
City
North Chicago
State
IL
Country
United States
Zip Code
60064
Wong, Wai Chong; Marinelli, Michela (2016) Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking. Addict Biol 21:634-45
Wong, Wai Chong; Ford, Kerstin A; Pagels, Nicole E et al. (2013) Adolescents are more vulnerable to cocaine addiction: behavioral and electrophysiological evidence. J Neurosci 33:4913-22
McCutcheon, James E; Conrad, Kelly L; Carr, Steven B et al. (2012) Dopamine neurons in the ventral tegmental area fire faster in adolescent rats than in adults. J Neurophysiol 108:1620-30
McCutcheon, James E; Loweth, Jessica A; Ford, Kerstin A et al. (2011) Group I mGluR activation reverses cocaine-induced accumulation of calcium-permeable AMPA receptors in nucleus accumbens synapses via a protein kinase C-dependent mechanism. J Neurosci 31:14536-41
McCutcheon, James E; Wang, Xiaoting; Tseng, Kuei Y et al. (2011) Calcium-permeable AMPA receptors are present in nucleus accumbens synapses after prolonged withdrawal from cocaine self-administration but not experimenter-administered cocaine. J Neurosci 31:5737-43
Conrad, Kelly L; McCutcheon, James E; Cotterly, Lindsay M et al. (2010) Persistent increases in cocaine-seeking behavior after acute exposure to cold swim stress. Biol Psychiatry 68:303-5
Steiner, Heinz; Van Waes, Vincent; Marinelli, Michela (2010) Fluoxetine potentiates methylphenidate-induced gene regulation in addiction-related brain regions: concerns for use of cognitive enhancers? Biol Psychiatry 67:592-4
Zahm, Daniel S; Becker, Mary L; Freiman, Alexander J et al. (2010) Fos after single and repeated self-administration of cocaine and saline in the rat: emphasis on the Basal forebrain and recalibration of expression. Neuropsychopharmacology 35:445-63
Conrad, K L; Ford, K; Marinelli, M et al. (2010) Dopamine receptor expression and distribution dynamically change in the rat nucleus accumbens after withdrawal from cocaine self-administration. Neuroscience 169:182-94
Van Waes, Vincent; Beverley, Joel; Marinelli, Michela et al. (2010) Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum. Eur J Neurosci 32:435-47

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