Dopamine transporter mRNA is up-regulated in the substantia nigra and the ventral tegmental area of amphetamine-sensitized rats.
Converging evidence supports a significant role for dopamine (DA) in the development of behavioral sensitization and it has been suggested that changes in either DA transporter (DAT) or D2 autoreceptors contribute to the effects of stimulant treatment. To determine if alterations in DAT or D2 autoreceptor mRNA are long-lasting and parallel the time course of amphetamine (AMPH)-induced behavioral sensitization we performed the following experiment. Two groups of rats were used for mRNA analysis by in situ hybridization. They were given either single daily injections of saline or AMPH (2.5 mg/kg) for 5 days and sacrificed 7 days later. Two groups pretreated in a similar manner were used to test for behavioral sensitization. Pretreatment with AMPH which resulted in a sensitization response profile after AMPH challenge also produced a significant up-regulation of DAT mRNA in both the ventral tegmental area (VTA) (P = 0.01) and substantia nigra (SN) (P < 0.05) compared to the saline controls, whereas there were no significant group differences in D2 mRNA in either the SN or the VTA. The possible role of these changes in behavioral sensitization is discussed.
Shilling
P D
PD
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093-0603, USA.
Kelsoe
J R
JR
Segal
D S
DS
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004361:Drug Tolerance; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; C493216:Slc6a3 protein, rat; D000661:Amphetamine