RGD Reference Report - Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning. - Rat Genome Database

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Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning.

Authors: King, C P  Militello, L  Hart, A  St Pierre, C L  Leung, E  Versaggi, C L  Roberson, N  Catlin, J  Palmer, A A  Richards, J B  Meyer, P J 
Citation: King CP, etal., Genes Brain Behav. 2017 Sep;16(7):686-698. doi: 10.1111/gbb.12382. Epub 2017 May 2.
RGD ID: 13503340
Pubmed: PMID:28387990   (View Abstract at PubMed)
PMCID: PMC5595635   (View Article at PubMed Central)
DOI: DOI:10.1111/gbb.12382   (Journal Full-text)

Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knockout (KO) rats and AdipoQ KO mice using intravenous cocaine self-administration and conditioned place preference (CPP) paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/-) and KO (-/-) rats showed increased cue-induced reinstatement compared with wild-type (WT) rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 -/- rats showed higher responding for a saccharin reinforcer and learned the choice reaction time (RT) task more slowly than WTs. However, we found no differences between Cdh13 -/- and +/+ rats in responding for sensory reinforcement, number of premature responses in the RT task, tendency to approach a Pavlovian food cue, CPP and locomotor activation to cocaine (10 or 20¿mg/kg). In AdipoQ -/- mice, there was a significant increase in CPP to methamphetamine (1¿mg/kg) but not to a range of d-amphetamine doses (0.5, 1, 2 and 4¿mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CDH13Humansubstance-related disorder  ISOCdh13 (Rattus norvegicus) RGD 
Cdh13Ratsubstance-related disorder  IMP  RGD 
Cdh13Mousesubstance-related disorder  ISOCdh13 (Rattus norvegicus) RGD 
Cdh13em1McwiRatsubstance-related disorder  IMP knock-out compared to wild-type ratsRGD 
SS-Cdh13em1Mcwi-/-Ratsubstance-related disorder  IMP  RGD 
SS-Cdh13em1McwiRatsubstance-related disorder  IMP knock-out compared to wild-type ratsRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cdh13Ratabnormal cue-induced reinstatement of an extinguished operant behavior for a cocaine reinforcer  IMP knock-out compared to wild-type ratsRGD 
Cdh13em1McwiRatabnormal cue-induced reinstatement of an extinguished operant behavior for a cocaine reinforcer  IMP knock-out compared to wild-type ratsRGD 
SS-Cdh13em1Mcwi-/-Ratabnormal cue-induced reinstatement of an extinguished operant behavior for a cocaine reinforcer  IMP knock-out compared to wild-type ratsRGD 
SS-Cdh13em1McwiRatabnormal cue-induced reinstatement of an extinguished operant behavior for a cocaine reinforcer  IMP knock-out compared to wild-type ratsRGD 
Cdh13Ratsaccharin preference  IMP knock-out compared to wild-type ratsRGD 
Cdh13em1McwiRatsaccharin preference  IMP knock-out compared to wild-type ratsRGD 
SS-Cdh13em1McwiRatsaccharin preference  IMP knock-out compared to wild-type ratsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Cdh13  (cadherin 13)
Cdh13em1Mcwi  (cadherin 13; zinc finger nuclease induced mutant 1, Medical College of Wisconsin)

Genes (Mus musculus)
Cdh13  (cadherin 13)

Genes (Homo sapiens)
CDH13  (cadherin 13)

Strains
SS-Cdh13em1Mcwi-/-  (SS-Cdh13em1Mcwi-/Cdh13em1Mcwi-)
SS-Cdh13em1Mcwi  (NA)


Additional Information