PMID- 28025973
OWN - NLM
STAT- MEDLINE
DCOM- 20180108
LR  - 20191210
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 42
IP  - 5
DP  - 2017 Apr
TI  - Lateral Habenula Involvement in Impulsive Cocaine Seeking.
PG  - 1103-1112
LID - 10.1038/npp.2016.286 [doi]
AB  - The lateral habenula (LHb) is a brain structure receiving inputs from limbic 
      forebrain areas and innervating major midbrain monoaminergic nuclei. Evidence 
      indicates LHb involvement in sleep control, reward-based decision making, 
      avoidance of punishment, and responses to stress. Additional work has established 
      that the LHb mediates negative feedback in response to aversive events. As a 
      hallmark of drug addiction is the inability to limit drug use despite negative 
      consequences, we hypothesize that LHb dysfunction may have a role in the lack of 
      control over drug seeking. Here we examine the effects of LHb inactivation in 
      control over drug seeking in several cocaine self-administration (SA) paradigms 
      in rats. We find that inhibition of the LHb with GABAergic agonists did not alter 
      cocaine SA under progressive ratio or seeking/taking chained reinforcement 
      schedules, or during punishment-induced suppression of cocaine-reinforced 
      responding. In contrast, LHb inhibition increased cocaine seeking when the drug 
      was not available in rats trained to discriminate its presence using an 
      environmental cue. This effect of LHb inhibition was selective for cocaine, as it 
      did not impair responding for sucrose reinforcement. The effect of LHb injection 
      of GABA agonists was mimicked by intra-LHb muscarinic cholinergic (mACh) 
      antagonist injection, and activation of mACh receptors excited a majority of LHb 
      neurons in in vitro electrophysiology experiments. These results indicate that 
      the LHb participates in the suppression of impulsive responding for cocaine 
      through the activation of a cholinergic circuit, and they suggest that LHb 
      dysfunction may contribute to impaired impulse control associated with drug 
      addiction.
FAU - Zapata, Agustin
AU  - Zapata A
AD  - Electrophysiology Research Section, Cellular Neurobiology Branch, National 
      Institutes of Health, National Institute on Drug Abuse, Intramural Research 
      Program, Baltimore, MD, USA.
FAU - Hwang, Eun-Kyung
AU  - Hwang EK
AD  - Electrophysiology Research Section, Cellular Neurobiology Branch, National 
      Institutes of Health, National Institute on Drug Abuse, Intramural Research 
      Program, Baltimore, MD, USA.
FAU - Lupica, Carl R
AU  - Lupica CR
AD  - Electrophysiology Research Section, Cellular Neurobiology Branch, National 
      Institutes of Health, National Institute on Drug Abuse, Intramural Research 
      Program, Baltimore, MD, USA.
LA  - eng
PT  - Journal Article
DEP - 20161227
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (GABA-A Receptor Agonists)
RN  - 0 (GABA-B Receptor Agonists)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Receptors, GABA)
RN  - 0 (Receptors, Muscarinic)
RN  - 2763-96-4 (Muscimol)
RN  - H789N3FKE8 (Baclofen)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Baclofen/administration & dosage
MH  - Cocaine/*administration & dosage
MH  - Conditioning, Operant/drug effects/physiology
MH  - Drug-Seeking Behavior/*drug effects
MH  - Electroshock
MH  - GABA-A Receptor Agonists/administration & dosage
MH  - GABA-B Receptor Agonists/administration & dosage
MH  - Habenula/*drug effects/*physiology
MH  - Impulsive Behavior/*drug effects/physiology
MH  - Male
MH  - Motivation/drug effects/physiology
MH  - Muscarinic Agonists/administration & dosage
MH  - Muscimol/administration & dosage
MH  - Punishment
MH  - Rats, Long-Evans
MH  - Receptors, GABA/physiology
MH  - Receptors, Muscarinic/physiology
MH  - Reinforcement, Psychology
MH  - Self Administration
PMC - PMC5506796
EDAT- 2016/12/28 06:00
MHDA- 2018/01/09 06:00
PMCR- 2018/04/01
CRDT- 2016/12/28 06:00
PHST- 2016/09/16 00:00 [received]
PHST- 2016/12/13 00:00 [revised]
PHST- 2016/12/19 00:00 [accepted]
PHST- 2016/12/28 06:00 [pubmed]
PHST- 2018/01/09 06:00 [medline]
PHST- 2016/12/28 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - npp2016286 [pii]
AID - 10.1038/npp.2016.286 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2017 Apr;42(5):1103-1112. doi: 10.1038/npp.2016.286. 
      Epub 2016 Dec 27.