PMID- 31062481
OWN - NLM
STAT- MEDLINE
DCOM- 20210624
LR  - 20210624
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Linking)
VI  - 25
IP  - 3
DP  - 2020 May
TI  - Increased relapse to cocaine-seeking in a genetic model for depression.
PG  - e12756
LID - 10.1111/adb.12756 [doi]
AB  - The greatest difficulty in treating cocaine addiction is the enormous rates of 
      relapse, which occur despite immense negative consequences. Relapse risks are 
      even greater in addicts with comorbid depression, perhaps because they use drugs 
      to alleviate depressive symptoms. Only a few preclinical studies have examined 
      this comorbidity, mostly exploring depressive-like effects following drug 
      exposure. We examined rats from two different depression-like models: (a) 
      chronic-mild-stress (CMS), which respond to antidepressant medications and (b) 
      depressed-rat-line (DRL), a genetic model of selective breeding, which is less 
      responsive to antidepressant medications. We tested addictive behaviors in a 
      cocaine self-administration procedure, including the "conflict model," where 
      drug-seeking and relapse encounter adverse consequences: an electrified grid in 
      front of the drug-delivering lever. Following behavioral testing, we explored a 
      potential association between behavioral outcomes and protein expression of 
      brain-derived neurotrophic factor (BDNF). We found that DRL rats self-administer 
      more cocaine compared with both CMS and controls, while CMS and control groups 
      did not differ significantly. Notably, DRL but not CMS rats, displayed higher 
      rates of relapse than controls, and expressed higher levels of BDNF in the 
      prelimbic cortex (PLC). Potential translation of these results suggest that 
      medication-resistant depressed patients tend to consume more drugs and are more 
      susceptible to relapse. The increase in PLC BDNF levels is consistent with 
      previous rat models of depression, and concomitantly, with its suggested role in 
      promoting cocaine-seeking.
CI  - (c) 2019 Society for the Study of Addiction.
FAU - Zilkha, Noga
AU  - Zilkha N
AUID- ORCID: 0000-0003-4650-766X
AD  - Department of Neurobiology, Weizmann institute of Science, Rehovot, Israel.
AD  - Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion 
      University, Be'er Sheva, Israel.
FAU - Barnea-Ygael, Noam
AU  - Barnea-Ygael N
AD  - Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion 
      University, Be'er Sheva, Israel.
FAU - Keidar, Liraz
AU  - Keidar L
AD  - Department of Neurobiology, Weizmann institute of Science, Rehovot, Israel.
FAU - Zangen, Abraham
AU  - Zangen A
AD  - Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion 
      University, Be'er Sheva, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190507
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (Antidepressive Agents)
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Behavior, Animal/drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cocaine/*administration & dosage
MH  - Depression/genetics/physiopathology/*psychology
MH  - Depressive Disorder, Treatment-Resistant/genetics/physiopathology/*psychology
MH  - Disease Models, Animal
MH  - Dopamine Uptake Inhibitors/*administration & dosage
MH  - Drug-Seeking Behavior/drug effects/*physiology
MH  - Prefrontal Cortex/*physiopathology
MH  - Rats
MH  - Recurrence
MH  - Self Administration
MH  - Stress, Psychological/physiopathology/*psychology
OTO - NOTNLM
OT  - BDNF
OT  - cocaine
OT  - depression
OT  - genetic-model
OT  - relapse
OT  - self-administration
EDAT- 2019/05/08 06:00
MHDA- 2021/06/25 06:00
CRDT- 2019/05/08 06:00
PHST- 2018/11/13 00:00 [received]
PHST- 2019/02/21 00:00 [revised]
PHST- 2019/03/18 00:00 [accepted]
PHST- 2019/05/08 06:00 [pubmed]
PHST- 2021/06/25 06:00 [medline]
PHST- 2019/05/08 06:00 [entrez]
AID - 10.1111/adb.12756 [doi]
PST - ppublish
SO  - Addict Biol. 2020 May;25(3):e12756. doi: 10.1111/adb.12756. Epub 2019 May 7.