D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats.
Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, and locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects and in non human primates after chronic cocaine exposures. Prior studies had shown that D2R upregulation in the nucleus accumbens (NAc) in rodents trained to self-administer alcohol markedly attenuated alcohol preference and intake. Here we assess the effects of D2R upregulation in the NAc on cocaine intake in rats trained to self-administer cocaine. Following 2 weeks of i.v. cocaine self-administration (CSA), rats were stereotaxically treated with an adenovirus that carried the D2R gene to upregulate D2R in the NAc. D2R vector treatment resulted in a significant decrease (75%) in cocaine infusions and lever presses (70%) for cocaine. This effect lasted 6 days before cocaine consumption returned to baseline levels, which corresponds roughly to the time it takes D2R to return to baseline levels. These findings show that CSA and D2R in the NAc are negatively correlated and suggest that cocaine intake is modulated in part by D2R levels in NAc. Thus strategies aimed at increasing D2R expression in NAc may be beneficial in treating cocaine abuse and addiction.
Thanos
Panayotis K
PK
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. thanos@bnl.gov
Michaelides
Michael
M
Umegaki
Hiroyuki
H
Volkow
Nora D
ND
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D004247:DNA / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000235:genetics*; D012201:Reward; D012646:Self Administration; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics
D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D004247:DNA; D003042:Cocaine; D004298:Dopamine