The use of cocaine and amphetamines remains a global problem. Drug addiction involves the complicated interplay between genetics, environment and neuronal changes. Studies have shown that stress, primarily social stress, has a robust correlation with drug abuse, increasing the likelihood of addiction, craving and relapse. Investigation of the cellular changes involved in sensitization to social stress and psychostimulants will shed light on the mechanisms modulating addictive processes. The studies proposed in this fellowship application will examine the dialogue between genes and environment and the impact this has on sensitivity to cocaine and amphetamine by using C57BL/6 and DBA/2 mice, two strains divergent on numerous phenotypes, in experiments of social defeat stress sensitization and subsequent psychostimulant sensitization and cocaine self-administration.
The second aim of this proposal is to characterize the underlying neural adaptations that occur in the social defeat stress-sensitized animal, using imunohistochemical techniques. The medial prefrontal cortex has been implicated in both stress and reward. Clarifying the role of the serotonergic pathway from the dorsal raphe nucleus to the medial prefrontal cortex in stress and addiction may lead to the development of pharmaceutical agents in the treatment of psychostimulant addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA018478-01
Application #
6835965
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Lawrence, Diane M
Project Start
2004-09-30
Project End
2007-09-29
Budget Start
2004-09-30
Budget End
2005-09-29
Support Year
1
Fiscal Year
2004
Total Cost
$23,522
Indirect Cost
Name
Tufts University
Department
Pharmacology
Type
Schools of Arts and Sciences
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
Yap, Jasmine J; Chartoff, Elena H; Holly, Elizabeth N et al. (2015) Social defeat stress-induced sensitization and escalated cocaine self-administration: the role of ERK signaling in the rat ventral tegmental area. Psychopharmacology (Berl) 232:1555-69
Yap, Jasmine J; Miczek, Klaus A (2007) Social defeat stress, sensitization, and intravenous cocaine self-administration in mice. Psychopharmacology (Berl) 192:261-73
Yap, Jasmine J; Takase, Luiz F; Kochman, Linda J et al. (2006) Repeated brief social defeat episodes in mice: effects on cell proliferation in the dentate gyrus. Behav Brain Res 172:344-50