PMID- 18256264
OWN - NLM
STAT- MEDLINE
DCOM- 20080225
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 28
IP  - 6
DP  - 2008 Feb 6
TI  - Cue-elicited reward-seeking requires extracellular signal-regulated kinase 
      activation in the nucleus accumbens.
PG  - 1434-43
LID - 10.1523/JNEUROSCI.2383-07.2008 [doi]
AB  - The motivation to seek out rewards can come under the control of stimuli 
      associated with reward delivery. The ability of cues to motivate reward-seeking 
      behavior depends on the nucleus accumbens (NAcc). The molecular mechanisms in the 
      NAcc that underlie the ability of a cue to motivate reward-seeking are not well 
      understood. We examined whether extracellular signal-regulated kinase (ERK), an 
      important intracellular signaling pathway in learning and memory, has a role in 
      these motivational processes. We first examined p42 ERK (ERK2) activation in the 
      NAcc after rats were trained to associate an auditory stimulus with food delivery 
      and found that, as a consequence of training, presentation of the auditory cue 
      itself was sufficient to increase ERK2 activation in the NAcc. To examine whether 
      inhibition of ERK in the NAcc prevents cue-induced reward-seeking, we infused an 
      inhibitor of ERK, U0126, into the NAcc before assessing rats' instrumental 
      responding in the presence versus absence of the conditioned cue. We found that, 
      whereas vehicle-infused rats showed increased instrumental responding during cue 
      presentation, rats infused with U0126 showed a profound impairment in cue-induced 
      instrumental responding. In contrast, intra-NAcc U0126 infusion had no effect on 
      rats' food-reinforced instrumental responding or their ability to execute 
      conditioned approach behavior. Our results demonstrate learning-related changes 
      in ERK signaling in the NAcc, and that disruption of ERK activation in this 
      structure interferes with the incentive-motivational effects of conditioned 
      stimuli. The molecular mechanisms described here may have implications for 
      cue-elicited drug craving after repeated exposure to drugs of abuse.
FAU - Shiflett, Michael W
AU  - Shiflett MW
AD  - Department of Neurobiology, Center for the Neural Basis of Cognition, University 
      of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
FAU - Martini, Ross P
AU  - Martini RP
FAU - Mauna, Jocelyn C
AU  - Mauna JC
FAU - Foster, Rebecca L
AU  - Foster RL
FAU - Peet, Eloise
AU  - Peet E
FAU - Thiels, Edda
AU  - Thiels E
LA  - eng
GR  - NIDA F32019431/PHS HHS/United States
GR  - NINDS T3207391/PHS HHS/United States
GR  - R01 NS046423/NS/NINDS NIH HHS/United States
GR  - R01 NS046423-04/NS/NINDS NIH HHS/United States
GR  - NINDS R01046423/PHS HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
CIN - J Neurosci. 2008 Apr 23;28(17):4295-7. PMID: 18434506
MH  - Animals
MH  - Conditioning, Psychological/physiology
MH  - *Cues
MH  - Enzyme Activation/physiology
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Male
MH  - Nucleus Accumbens/*enzymology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Reward
PMC - PMC2670997
MID - NIHMS96494
EDAT- 2008/02/08 09:00
MHDA- 2008/02/26 09:00
PMCR- 2008/08/06
CRDT- 2008/02/08 09:00
PHST- 2008/02/08 09:00 [pubmed]
PHST- 2008/02/26 09:00 [medline]
PHST- 2008/02/08 09:00 [entrez]
PHST- 2008/08/06 00:00 [pmc-release]
AID - 28/6/1434 [pii]
AID - 3313285 [pii]
AID - 10.1523/JNEUROSCI.2383-07.2008 [doi]
PST - ppublish
SO  - J Neurosci. 2008 Feb 6;28(6):1434-43. doi: 10.1523/JNEUROSCI.2383-07.2008.