PMID- 24118426
OWN - NLM
STAT- MEDLINE
DCOM- 20150824
LR  - 20211021
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Print)
IS  - 1355-6215 (Linking)
VI  - 20
IP  - 1
DP  - 2015 Jan
TI  - Cocaine-elicited imbalances in ventromedial prefrontal cortex Homer1 versus 
      Homer2 expression: implications for relapse.
PG  - 148-57
LID - 10.1111/adb.12088 [doi]
AB  - Withdrawal from a history of extended access to self-administered cocaine 
      produces a time-dependent intensification of drug seeking, which might relate to 
      a cocaine-induced imbalance in the relative expression of constitutively 
      expressed Homer1 versus Homer2 isoforms within the ventromedial aspect of the 
      prefrontal cortex (vmPFC). Thus, we employed immunoblotting to examine the 
      relation between cue-reinforced lever pressing at 3- versus 30-day withdrawal 
      from a 10-day history of extended access (6 hours/day) to intravenous cocaine 
      (0.25 mg/infusion) or saline (Sal6h), and the expression of Homer1b/c and 
      Homer2a/b within the vmPFC versus the more dorsomedial aspect of this structure 
      (dmPFC). Behavioral studies employed adeno-associated virus (AAV) vectors to 
      reverse cocaine-elicited changes in the relative expression of Homer1 versus 
      Homer2 isoforms and tested animals for cocaine prime-, and cue-induced responding 
      following extinction training. Cocaine self-administration elevated both 
      Homer1b/c and Homer2a/b levels within the vmPFC at 3-day withdrawal, and the rise 
      in Homer2a/b persisted for at least 30 days. dmPFC Homer levels did not change as 
      a function of self-administration history. Reversing the relative increase in 
      Homer2 versus Homer1 expression via Homer1c overexpression or Homer2b knockdown 
      failed to influence cue-reinforced lever pressing when animals were tested in a 
      drug-free state, but both AAV treatments prevented cocaine-primed reinstatement 
      of lever-pressing behavior. These data suggest that a cocaine-elicited imbalance 
      in the relative expression of constitutively expressed Homer2 versus Homer1 
      within the vmPFC is necessary for the capacity of cocaine to reinstate 
      drug-seeking behavior, posing drug-induced changes in vmPFC Homer expression as a 
      molecular trigger contributing to drug-elicited relapse.
CI  - (c) 2013 Society for the Study of Addiction.
FAU - Gould, Adam T
AU  - Gould AT
AD  - Department of Psychological and Brain Sciences and the Neuroscience Research 
      Institute, University of California at Santa Barbara, Santa Barbara, CA, USA.
FAU - Sacramento, Arianne D
AU  - Sacramento AD
FAU - Wroten, Melissa G
AU  - Wroten MG
FAU - Miller, Bailey W
AU  - Miller BW
FAU - von Jonquieres, Georg
AU  - von Jonquieres G
FAU - Klugmann, Matthias
AU  - Klugmann M
FAU - Ben-Shahar, Osnat
AU  - Ben-Shahar O
FAU - Szumlinski, Karen K
AU  - Szumlinski KK
LA  - eng
GR  - R01 DA024038/DA/NIDA NIH HHS/United States
GR  - DA024038/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130930
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (Carrier Proteins)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Homer Scaffolding Proteins)
RN  - 0 (Homer1 protein, rat)
RN  - 0 (Homer2 protein, rat)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*drug effects/metabolism
MH  - Cocaine/*pharmacology
MH  - Cocaine-Related Disorders/*metabolism
MH  - Dopamine Uptake Inhibitors/*pharmacology
MH  - Drug-Seeking Behavior/*drug effects/physiology
MH  - Homer Scaffolding Proteins
MH  - Prefrontal Cortex/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recurrence
PMC - PMC3969898
MID - NIHMS519614
OTO - NOTNLM
OT  - Addiction
OT  - Homer proteins
OT  - craving
OT  - prefrontal cortex
OT  - reinstatement
OT  - self-administration
COIS- Conflict of Interest None of the authors have any conflict of interest to declare 
      with respect to the research presented in this report.
EDAT- 2013/10/15 06:00
MHDA- 2015/08/25 06:00
PMCR- 2016/01/01
CRDT- 2013/10/15 06:00
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2015/08/25 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.1111/adb.12088 [doi]
PST - ppublish
SO  - Addict Biol. 2015 Jan;20(1):148-57. doi: 10.1111/adb.12088. Epub 2013 Sep 30.