RGD Reference Report - Sexually dimorphic intracellular responses after cocaine-induced conditioned place preference expression. - Rat Genome Database

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Sexually dimorphic intracellular responses after cocaine-induced conditioned place preference expression.

Authors: Nygard, Stephanie K  Klambatsen, Anthony  Hazim, Ruhal  Eltareb, Mohamed H  Blank, Jeff C  Chang, Anna J  Quinones-Jenab, Vanya  Jenab, Shirzad 
Citation: Nygard SK, etal., Brain Res. 2013 Jul 3;1520:121-33. doi: 10.1016/j.brainres.2013.04.060. Epub 2013 May 9.
RGD ID: 401851078
Pubmed: PMID:23665060   (View Abstract at PubMed)
PMCID: PMC3964786   (View Article at PubMed Central)
DOI: DOI:10.1016/j.brainres.2013.04.060   (Journal Full-text)

Sex differences in cocaine's mechanisms of action and behavioral effects have been widely reported. However, little is known about how sex influences intracellular signaling cascades involved with drug-environment associations. We investigated whether ERK/CREB intracellular responses in the mesocorticolimbic circuitry underlying cocaine environmental associations are sexually dimorphic. We used a standard 4 day conditioned place preference (CPP) paradigm using 20mg/kg cocaine-a dose that induced CPP in male and female Fischer rats. In the nucleus accumbens (NAc) following CPP expression, cocaine treated animals showed increased phosphorylated ERK (pERK), phosphorylated CREB (pCREB) and ΔFosB protein levels. In the hippocampus (HIP) and caudate putamen (CPu), pERK and FosB/ΔFosB levels were also increased, respectively. Cocaine females had a larger change in HIP pERK and CPu ΔFosB levels than cocaine males; partly due to lower protein levels in saline female rats when compared to saline males. Prefrontal cortex (PfC) pCREB levels increased in cocaine males, but not females, whereas PfC pERK levels were increased in cocaine females, but not males. CPP scores were positively correlated to NAc pERK, HIP pERK and CPu FosB protein levels, suggesting that similar to males, the ERK/CREB intracellular pathway in mesocorticolimbic regions undergoes cocaine induced neuroplasticity in female rats. However, there seem to be intrinsic (basal) sexual dimorphisms in this pathway that may contribute to responses expressed after cocaine-CPP. Taken together, our results suggest that cellular responses associated with the expression of learned drug-environment associations may play an important role in sex differences in cocaine addiction and relapse.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CREB1Humancocaine dependence sexual_dimorphism ISOCreb1 (Rattus norvegicus)protein:increased phosphorylation:nucleus accumbens and prefrontal cortexRGD 
Creb1Ratcocaine dependence sexual_dimorphism IDA protein:increased phosphorylation:nucleus accumbens and prefrontal cortexRGD 
Creb1Mousecocaine dependence sexual_dimorphism ISOCreb1 (Rattus norvegicus)protein:increased phosphorylation:nucleus accumbens and prefrontal cortexRGD 
FOSBHumancocaine dependence  ISOFosb (Rattus norvegicus)protein:increased expression:Brain (rat)RGD 
FosbMousecocaine dependence  ISOFosb (Rattus norvegicus)protein:increased expression:Brain (rat)RGD 
FosbRatcocaine dependence  IEP protein:increased expression:Brain (rat)RGD 
MAPK1Humancocaine dependence  ISOMapk1 (Rattus norvegicus)protein:increased phosphorylation:brainRGD 
MAPK3Humancocaine dependence  ISOMapk3 (Rattus norvegicus)protein:increased phosphorylation:brainRGD 
Mapk1Ratcocaine dependence  IDA protein:increased phosphorylation:brainRGD 
Mapk1Mousecocaine dependence  ISOMapk1 (Rattus norvegicus)protein:increased phosphorylation:brainRGD 
Mapk3Ratcocaine dependence  IDA protein:increased phosphorylation:brainRGD 
Mapk3Mousecocaine dependence  ISOMapk3 (Rattus norvegicus)protein:increased phosphorylation:brainRGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FOSBHumancocaine increases expression ISOFosb (Rattus norvegicus)cocaine increases expression of Fosb protein in Brain RGD 
FosbRatcocaine increases expression EXP cocaine increases expression of Fosb protein in Brain RGD 
FosbMousecocaine increases expression ISOFosb (Rattus norvegicus)cocaine increases expression of Fosb protein in Brain RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FosbRatresponse to cocaine  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Creb1  (cAMP responsive element binding protein 1)
Fosb  (FosB proto-oncogene, AP-1 transcription factor subunit)
Mapk1  (mitogen activated protein kinase 1)
Mapk3  (mitogen activated protein kinase 3)

Genes (Mus musculus)
Creb1  (cAMP responsive element binding protein 1)
Fosb  (FBJ osteosarcoma oncogene B)
Mapk1  (mitogen-activated protein kinase 1)
Mapk3  (mitogen-activated protein kinase 3)

Genes (Homo sapiens)
CREB1  (cAMP responsive element binding protein 1)
FOSB  (FosB proto-oncogene, AP-1 transcription factor subunit)
MAPK1  (mitogen-activated protein kinase 1)
MAPK3  (mitogen-activated protein kinase 3)


Additional Information