Repeated social defeat stress-induced sensitization to the locomotor activating effects of d-amphetamine: role of individual differences.
BACKGROUND
In this study, we sought to examine individual differences in stress-induced behavioral sensitization to d-amphetamine after repeated social defeat stress. In an effort to understand what mechanisms underlie stress-induced sensitization to d-amphetamine, we examined striatal gene expression of the dopamine receptor D(2). Additionally, we investigated if repeated social defeat was associated with changes in dendritic spine density in the hippocampus, prefrontal cortex, and nucleus accumbens of rats that exhibit stress-induced sensitization.


METHODS
Male rats were classified into high responders (HR) and low responders (LR) based on their locomotor response to a novel environment. Then, rats were either handled as a control or defeated on four occasions by aggressive rats. Two weeks after the last defeat, animals were challenged with one of three doses of d-amphetamine and their locomotor activity was recorded.


RESULTS
Non-defeated HR rats exhibited higher locomotor activity in response to d-amphetamine when compared to LR non-defeated rats. Fourteen days from the last repeated social defeat, LR rats and HR rats were behaviorally identical in response to acute injections of amphetamine. Furthermore, HR non-defeated rats had less D(2) mRNA expression in the nucleus accumbens core and dorsal striatum than do LR non-defeated rats. However, after repeated social defeat, HR and LR rats had identical D(2) mRNA expression in both the core and dorsal striatum. Finally, there were no changes in dendritic spine density in any of the brain areas examined in LR rats.


CONCLUSIONS
Repeated social defeat abolishes individual differences in behavioral responses to d-amphetamine which may be due to a down-regulation of striatal dopamine D(2) receptors in LR rats.
Dietz
D M
DM
Department of Biomedical Sciences, Program in Neuroscience, Florida State University, Tallahassee, FL, 32306, USA.
Dietz
K C
KC
Moore
S
S
Ouimet
C C
CC
Kabbaj
M
M
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D049229:Dendritic Spines / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D017403:In Situ Hybridization; D007206:Individuality; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000187:drug effects; D012930:Social Dominance; D013315:Stress, Psychological / Q000523:psychology*
D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D003913:Dextroamphetamine