PMID- 14668941
OWN - NLM
STAT- MEDLINE
DCOM- 20040308
LR  - 20191108
IS  - 0214-0934 (Print)
IS  - 0214-0934 (Linking)
VI  - 16
IP  - 7
DP  - 2003 Sep
TI  - Possible involvement of the ERK signaling cascade in bipolar disorder: behavioral 
      leads from the study of mutant mice.
PG  - 453-63
AB  - Despite the devastating impact that bipolar disorder has on the lives of millions 
      worldwide, little is known for certain about its etiology or pathophysiology. 
      Whereas research has traditionally focused on biogenic amines, it is becoming 
      increasingly more apparent that intracellular pathways are involved in the 
      etiology and treatment of the disease and that a true understanding of the 
      pathophysiology of bipolar disorder must address its neurobiology at different 
      physiological levels, that is, molecular, cellular, systems and behavioral 
      levels. There is now considerable biochemical evidence that the antimanic agents 
      lithium and valproate robustly activate the ERK signaling cascade in 
      therapeutically relevant paradigms. This raises the possibility that this pathway 
      may play a role in the antimanic effects of these agents. The present paper 
      reviews behavioral studies that may shed light on the involvement of the ERK 
      pathway in affective-like behaviors in animals. The available literature suggests 
      that genetic manipulations of the brain-derived neurotrophic factor (BDNF)-ERK 
      kinase pathway produces a variety of changes in affective-like behaviors, with 
      most changes consistent with manic-like behavior. Thus, overall, mice with 
      targeted mutation of the BDNF gene exhibited increased spontaneous locomotion and 
      increased response to acute amphetamine, altered response to chronic cocaine, 
      increased aggression, increase in risk-taking behavior, as demonstrated by time 
      spent in the center of an open field, and changes in eating patterns. Although it 
      has to be acknowledged that the currently available behavioral data from the 
      BDNF-ERK pathway mutants is less than ideal to offer real substantiation relating 
      this pathway to bipolar disorder, the data still supports the possibility that 
      this pathway modulates manic-like behavior in animals, and perhaps mania in 
      humans.
FAU - Einat, H
AU  - Einat H
AD  - Laboratory of Molecular Pathophysiology, National Institute of Mental Health, 
      National Institutes of Health, Department of Health and Human Services, Bethesda, 
      Maryland 20892-4405, USA. einath@intra.nimh.nih.gov
FAU - Manji, H K
AU  - Manji HK
FAU - Gould, T D
AU  - Gould TD
FAU - Du, J
AU  - Du J
FAU - Chen, G
AU  - Chen G
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Drug News Perspect
JT  - Drug news & perspectives
JID - 8809164
RN  - 614OI1Z5WI (Valproic Acid)
RN  - 9FN79X2M3F (Lithium)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects/*physiology
MH  - Bipolar Disorder/drug therapy/*genetics/*physiopathology
MH  - Humans
MH  - Lithium/therapeutic use
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - Signal Transduction/drug effects/genetics/*physiology
MH  - Valproic Acid/therapeutic use
RF  - 91
EDAT- 2003/12/12 05:00
MHDA- 2004/03/09 05:00
CRDT- 2003/12/12 05:00
PHST- 2003/12/12 05:00 [pubmed]
PHST- 2004/03/09 05:00 [medline]
PHST- 2003/12/12 05:00 [entrez]
AID - 414 [pii]
AID - 10.1358/dnp.2003.16.7.829357 [doi]
PST - ppublish
SO  - Drug News Perspect. 2003 Sep;16(7):453-63. doi: 10.1358/dnp.2003.16.7.829357.