PMID- 17292868
OWN - NLM
STAT- MEDLINE
DCOM- 20070613
LR  - 20181113
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1142
DP  - 2007 Apr 20
TI  - The adenosine A2A receptor agonist, CGS-21680, blocks excessive rearing, 
      acquisition of wheel running, and increases nucleus accumbens CREB 
      phosphorylation in chronically food-restricted rats.
PG  - 100-9
AB  - Adenosine A(2A) receptors are preferentially expressed in rat striatum, where 
      they are concentrated in dendritic spines of striatopallidal medium spiny neurons 
      and exist in a heteromeric complex with D(2) dopamine (DA) receptors. Behavioral 
      and biochemical studies indicate an antagonistic relationship between A(2A) and 
      D(2) receptors. Previous studies have demonstrated that food-restricted (FR) rats 
      display behavioral and striatal cellular hypersensitivity to D(1) and D(2) DA 
      receptor stimulation. These alterations may underlie adaptive, as well as 
      maladaptive, behaviors characteristic of the FR rat. The present study examined 
      whether FR rats are hypersensitive to the A(2A) receptor agonist, CGS-21680. In 
      Experiment 1, spontaneous horizontal motor activity did not differ between FR and 
      ad libitum fed (AL) rats, while vertical activity was greater in the former. 
      Intracerebroventricular (i.c.v.) administration of CGS-21680 (0.25 and 1.0 nmol) 
      decreased both types of motor activity in FR rats, and returned vertical activity 
      levels to those observed in AL rats. In Experiment 2, FR rats given access to a 
      running wheel for a brief period outside of the home cage rapidly acquired wheel 
      running while AL rats did not. Pretreatment with CGS-21680 (1.0 nmol) blocked the 
      acquisition of wheel running. When administered to FR subjects that had 
      previously acquired wheel running, CGS-21680 suppressed the behavior. In 
      Experiment 3, CGS-21680 (1.0 nmol) activated both ERK 1/2 and CREB in 
      caudate-putamen with no difference between feeding groups. However, in nucleus 
      accumbens (NAc), CGS-21680 failed to activate ERK 1/2 and selectively activated 
      CREB in FR rats. These results indicate that FR subjects are hypersensitive to 
      several effects of an adenosine A(2A) agonist, and suggest the involvement of an 
      upregulated A(2A) receptor-linked signaling pathway in NAc. Medications targeting 
      the A(2A) receptor may have utility in the treatment of maladaptive behaviors 
      associated with FR, including substance abuse and compulsive exercise.
FAU - Cabeza de Vaca, Soledad
AU  - Cabeza de Vaca S
AD  - Department of Psychiatry, New York University School of Medicine, New York, NY 
      10016, USA.
FAU - Kannan, Pavitra
AU  - Kannan P
FAU - Pan, Yan
AU  - Pan Y
FAU - Jiang, Nancy
AU  - Jiang N
FAU - Sun, Yanjie
AU  - Sun Y
FAU - Carr, Kenneth D
AU  - Carr KD
LA  - eng
GR  - K01 DA13960/DA/NIDA NIH HHS/United States
GR  - DA00292/DA/NIDA NIH HHS/United States
GR  - T35 DK007421/DK/NIDDK NIH HHS/United States
GR  - K01 DA013960/DA/NIDA NIH HHS/United States
GR  - K02 DA000292/DA/NIDA NIH HHS/United States
GR  - DA03956/DA/NIDA NIH HHS/United States
GR  - T32 DA007254/DA/NIDA NIH HHS/United States
GR  - R01 DA003956/DA/NIDA NIH HHS/United States
GR  - T32 DA07254/DA/NIDA NIH HHS/United States
GR  - R56 DA003956/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070117
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Phenethylamines)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*analogs & derivatives/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology
MH  - Behavior, Animal
MH  - CREB-Binding Protein/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - *Food Deprivation
MH  - Injections, Intraventricular/methods
MH  - Male
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Motor Activity/drug effects
MH  - Nucleus Accumbens/*drug effects/metabolism
MH  - Phenethylamines/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Running
PMC - PMC1868560
MID - NIHMS20907
EDAT- 2007/02/13 09:00
MHDA- 2007/06/15 09:00
PMCR- 2008/04/20
CRDT- 2007/02/13 09:00
PHST- 2006/12/19 00:00 [received]
PHST- 2007/01/10 00:00 [revised]
PHST- 2007/01/10 00:00 [accepted]
PHST- 2007/02/13 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/02/13 09:00 [entrez]
PHST- 2008/04/20 00:00 [pmc-release]
AID - S0006-8993(07)00129-1 [pii]
AID - 10.1016/j.brainres.2007.01.035 [doi]
PST - ppublish
SO  - Brain Res. 2007 Apr 20;1142:100-9. doi: 10.1016/j.brainres.2007.01.035. Epub 2007 
      Jan 17.