Reduction in dopamine transporter mRNA after cessation of repeated cocaine administration.
Male, Lewis rats were treated intravenously for 2 weeks with saline or cocaine using a dose and injection schedule that is similar to the doses and patterns of cocaine intake in self-administration studies. Ten days after cessation of treatment, dopamine transporter binding levels were decreased in the nucleus accumbens but not in the striatum. In situ hybridization studies revealed decreases in dopamine transporter mRNA that were restricted to cells of the interfascicular and caudal linear nuclei; these dopaminergic cell groups, found in the ventral tegmentum, project to the nucleus accumbens and other limbic areas. Other dopaminergic cell groups in midbrain which project mainly to other areas did not show a decrease in mRNA. These results indicate that gene expression can be altered many days after withdrawal from cocaine, and provide an example of transporter regulation by a change in gene expression.
NIH, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
C
C
Cerruti
N S
NS
Pilotte
G
G
Uhl
M J
MJ
Kuhar
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D004334:Drug Administration Schedule; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011485:Protein Binding; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D003042:Cocaine; D004298:Dopamine