It is believed that drugs of abuse usurp neural circuitry that initially evolved to mediate behavioral processes essential for fitness. Therefore, the take over of this circuitry by drugs of abuse usually exerts powerful control over the behavior and this is a tremendous problem for many humans. One important factor contributing to drug abuse is social environment. It has been suggested that social attachments formed in adulthood may have significant impact on drug addictions. Unfortunately, investigation into this topic is very limited partially because the vast majority of addiction research is conducted on traditional laboratory rats and mice that do not form adult-adult social attachments. Here we propose a novel line of research using a unique animal model to address fundamental questions regarding the interaction of social and drug reward and the underlying neural mechanisms. The monogamous prairie vole (Microtus ochrogaster) displays mating-induced pair bonding between mates, and this behavior is mediated by dopamine (DA) in the nucleus accumbens (NAcc). Recently, we also found that the prairie vole displays amphetamine (AMPH)-induced conditioned place preference (CPP) and pre-treatment of the DA receptor antagonist blocked this behavior. As natural reward and maladaptive drug reward are both regulated by DA, we hypothesized that these overlapping neural mechanisms will result in behavioral and neurobiological interactions between pair bonding and drug addiction. Here, we propose four studies by taking advantage of the vole model to systematically address interactions between pair bonding and drug reward and to study NAcc DA involvement in the regulation of such interactions.
In Specific Aim 1, we will firmly establish the vole model for drug reward by performing detailed dose response curves for AMPH induced CPP and behavioral sensitization.
In Specific Aim 2, we will examine NAcc DA involvement in AMPH reward.
In Specific Aim 3, we will study behavioral interactions between pair bonding and AMPH reward.
In Specific Aim 4, we will investigate the role of NAcc DA in the regulation of interactions between pair bonding and AMPH reward. Successful completion of these studies will further our understanding of behavioral and neurobiological interactions between social and drug reward, and such findings will have the potential to facilitate behavioral and neuropharmacological interventions that may aid addiction prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA019627-05
Application #
7587418
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (02))
Program Officer
Volman, Susan
Project Start
2005-04-01
Project End
2012-03-31
Budget Start
2009-04-01
Budget End
2012-03-31
Support Year
5
Fiscal Year
2009
Total Cost
$231,861
Indirect Cost
Name
Florida State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
790877419
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
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Young, Kimberly A; Liu, Yan; Gobrogge, Kyle L et al. (2014) Oxytocin reverses amphetamine-induced deficits in social bonding: evidence for an interaction with nucleus accumbens dopamine. J Neurosci 34:8499-506
Smith, Adam S; Wang, Zuoxin (2012) Salubrious effects of oxytocin on social stress-induced deficits. Horm Behav 61:320-30
Young, Kimberly A; Liu, Yan; Gobrogge, Kyle L et al. (2011) Amphetamine alters behavior and mesocorticolimbic dopamine receptor expression in the monogamous female prairie vole. Brain Res 1367:213-22
Young, Kimberly A; Gobrogge, Kyle L; Wang, Zuoxin (2011) The role of mesocorticolimbic dopamine in regulating interactions between drugs of abuse and social behavior. Neurosci Biobehav Rev 35:498-515
Young, Kimberly A; Gobrogge, Kyle L; Liu, Yan et al. (2011) The neurobiology of pair bonding: insights from a socially monogamous rodent. Front Neuroendocrinol 32:53-69
Liu, Yan; Young, Kimberly A; Curtis, J Thomas et al. (2011) Social bonding decreases the rewarding properties of amphetamine through a dopamine D1 receptor-mediated mechanism. J Neurosci 31:7960-6
Hollis, Fiona; Wang, Hui; Dietz, David et al. (2010) The effects of repeated social defeat on long-term depressive-like behavior and short-term histone modifications in the hippocampus in male Sprague-Dawley rats. Psychopharmacology (Berl) 211:69-77
Pan, Yongliang; Liu, Yan; Young, Kimberly A et al. (2009) Post-weaning social isolation alters anxiety-related behavior and neurochemical gene expression in the brain of male prairie voles. Neurosci Lett 454:67-71
Young, Kimberly A; Liu, Yan; Wang, Zuoxin (2008) The neurobiology of social attachment: A comparative approach to behavioral, neuroanatomical, and neurochemical studies. Comp Biochem Physiol C Toxicol Pharmacol 148:401-10

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