RGD Reference Report - Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats. - Rat Genome Database

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Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats.

Authors: St Laurent, Robyn  Helm, Samuel R  Glenn, Melissa J 
Citation: St Laurent R, etal., Neurosci Lett. 2013 Jun 7;544:94-9. doi: 10.1016/j.neulet.2013.03.050. Epub 2013 Apr 9.
RGD ID: 38501054
Pubmed: PMID:23583595   (View Abstract at PubMed)
PMCID: PMC3773519   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neulet.2013.03.050   (Journal Full-text)

Cocaine generates drug-seeking behavior by creating long-lasting changes in the reward pathway. The role of the growth factor, brain-derived neurotrophic factor (BDNF) in facilitating these changes was investigated in the present report with a genetic rat model. Using conditioned place preference, the current study investigated the hypothesis that a partial knockout of the BDNF gene in rats (BDNF(+/-)) would attenuate the rewarding effects of cocaine. Wildtype rats exposed to cocaine exhibited normal cocaine-seeking responses one day after conditioning and cocaine-seeking behavior was reinstated with drug priming following drug abstinence. In contrast, BDNF(+/-) rats did not show cocaine-seeking behavior one day after conditioning, nor did they respond to drug priming. A median split of rats based on BDNF levels in sera collected prior to behavioral procedures revealed that wildtype rats with high BDNF levels showed stronger conditioned place preference and reinstatement to cocaine. Together, the results support the hypothesis that a partial knockout of the BDNF gene attenuates the rewarding properties of cocaine. Additionally, individual differences in BDNF levels may predict future cocaine-seeking behavior. An underlying mechanism of these effects may be a reduction of the amount of synaptic changes made in the reward pathway.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BDNFHumanCocaine-Related Disorders severityISOBdnf (Rattus norvegicus) RGD 
BDNFHumanCocaine-Related Disorders susceptibilityISOBdnf (Rattus norvegicus) RGD 
BdnfRatCocaine-Related Disorders severityIMP  RGD 
BdnfRatCocaine-Related Disorders susceptibilityIMP  RGD 
BdnfMouseCocaine-Related Disorders severityISOBdnf (Rattus norvegicus) RGD 
BdnfMouseCocaine-Related Disorders susceptibilityISOBdnf (Rattus norvegicus) RGD 
Bdnfem1SageRatCocaine-Related Disorders severityIMP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BdnfRatbehavioral response to cocaine  IMP  RGD 
BdnfRatconditioned place preference  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BdnfRataddiction severityIMP  RGD 
BdnfRataddiction  IMP WT compared to heterozygous ratsRGD 
Bdnfem1SageRataddiction severityIMP  RGD 
BdnfRatcocaine preference severityIMP  RGD 
Bdnfem1SageRatcocaine preference severityIMP  RGD 
BdnfRatdecreased body weight  IMP WT compared to homozygous ratsRGD 
BdnfRathigh preference for an addictive substance amelioratesIMP WT compared to heterozygous ratsRGD 
Bdnfem1SageRathigh preference for an addictive substance amelioratesIMP WT compared to heterozygous ratsRGD 
SD-Bdnfem1Sage+/-Rathigh preference for an addictive substance amelioratesIMP WT compared to heterozygous ratsRGD 
BdnfRatimpaired conditioned place preference behavior  IMP compared to WTRGD 
Bdnfem1SageRatimpaired conditioned place preference behavior  IMP compared to WTRGD 
SD-Bdnfem1Sage+/-Ratimpaired conditioned place preference behavior  IMP compared to WTRGD 
BdnfRatincreased body weight severityIMP  RGD 
BdnfRatincreased body weight  IMP compared to WTRGD 
Bdnfem1SageRatincreased body weight  IMP compared to WTRGD 
Bdnfem1SageRatincreased body weight severityIMP  RGD 
SD-Bdnfem1Sage+/-Ratincreased body weight  IMP compared to WTRGD 
Objects Annotated

Genes (Rattus norvegicus)
Bdnf  (brain-derived neurotrophic factor)
Bdnfem1Sage  (brain-derived neurotrophic factor; ZFN induced mutant 1, Sage)

Genes (Mus musculus)
Bdnf  (brain derived neurotrophic factor)

Genes (Homo sapiens)
BDNF  (brain derived neurotrophic factor)

Strains
SD-Bdnfem1Sage+/-  (NA)


Additional Information