RGD Reference Report - Cocaine self-administration produces a persistent increase in dopamine D2 High receptors. - Rat Genome Database

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Cocaine self-administration produces a persistent increase in dopamine D2 High receptors.

Authors: Briand, LA  Flagel, SB  Seeman, P  Robinson, TE 
Citation: Briand LA, etal., Eur Neuropsychopharmacol. 2008 Aug;18(8):551-6. Epub 2008 Mar 4.
RGD ID: 2311586
Pubmed: PMID:18284941   (View Abstract at PubMed)
PMCID: PMC2527181   (View Article at PubMed Central)
DOI: DOI:10.1016/j.euroneuro.2008.01.002   (Journal Full-text)

Cocaine addicts are reported to have decreased numbers of striatal dopamine D2 receptors. However, in rodents, repeated cocaine administration consistently produces hypersensitivity to the psychomotor activating effects of both indirect dopamine agonists, such as cocaine itself, and importantly, to direct-acting D2 receptor agonists. The current study reports a possible resolution to this long-standing paradox. The dopamine D2 receptor exists in both a low and a high-affinity state, and dopamine exerts its effects via the more functionally relevant high-affinity D2 receptor (D2 High). We report here that cocaine self-administration experience produces a large (approximately 150%) increase in the proportion of D2 High receptors in the striatum with no change in the total number of D2 receptors, and this effect is evident both 3 and 30 days after the discontinuation of cocaine self-administration. Changes in D2 High receptors would not be evident with the probes used in human (and non-human primate) imaging studies. We suggest, therefore, that cocaine addicts and animals previously treated with cocaine may be hyper-responsive to dopaminergic drugs in part because an increase in D2 High receptors results in dopamine supersensitivity. This may also help explain why stimuli that increase dopamine neurotransmission, including drugs themselves, are so effective in producing relapse in individuals with a history of exposure to cocaine.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cocaine-Related Disorders  ISODrd2 (Rattus norvegicus)2311586; 2311586protein:increased activity:caudate putamen (rat)RGD 
Cocaine-Related Disorders  IDA 2311586protein:increased activity:caudate putamen (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Drd2  (dopamine receptor D2)

Genes (Mus musculus)
Drd2  (dopamine receptor D2)

Genes (Homo sapiens)
DRD2  (dopamine receptor D2)


Additional Information