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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cocaine-Related Disorders severityISOBdnf (Rattus norvegicus)38501054; 38501054 RGD 
Cocaine-Related Disorders susceptibilityISOBdnf (Rattus norvegicus)38501054; 38501054 RGD 
Cocaine-Related Disorders severityIMP 38501054; 38501054 RGD 
Cocaine-Related Disorders susceptibilityIMP 38501054 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
behavioral response to cocaine  IMP 38501054 RGD 
conditioned place preference  IMP 38501054 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
addiction severityIMP 38501054; 38501054 RGD 
addiction  IMP 38501054WT compared to heterozygous ratsRGD 
cocaine preference severityIMP 38501054; 38501054 RGD 
decreased body weight  IMP 38501054WT compared to homozygous ratsRGD 
high preference for an addictive substance amelioratesIMP 38501054; 38501054; 38501054WT compared to heterozygous ratsRGD 
impaired conditioned place preference behavior  IMP 38501054; 38501054; 38501054compared to WTRGD 
increased body weight severityIMP 38501054; 38501054 RGD 
increased body weight  IMP 38501054; 38501054; 38501054compared 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)

SD-Bdnfem1Sage+/-  (NA)

Additional Information