Dopaminergic gene expression during amphetamine withdrawal.
Animals and humans display a constellation of behavioral and neurochemical signs after termination of psychostimulant administration. Amphetamine withdrawal could involve the dopaminergic systems that are thought to underlie psychostimulant rewarding effects, and may thus conceivably alter expression of key genes for dopaminergic transmission, including those encoding tyrosine hydroxylase (TH), the membrane dopamine transporter (DAT) and the synaptic vesicle amine transporter (SVAT). Withdrawal from 7.5 mg kg-1 i.p. amphetamine (b.i.d. for a two week duration) yields no significant changes in rat DAT mRNA. TH mRNA levels are modestly enhanced over the same week of withdrawal, during which dopamine levels and behavioral novelty responses are both depressed. SVAT expression is significantly blunted following chronic amphetamine treatment. Altered TH and/or SVAT gene expression might contribute to restoring normal function to neurons "withdrawing" from amphetamine treatments.
Persico
A M
AM
Addiction Research Center, NIDA, Baltimore, MD 21224.
Schindler
C W
CW
Brannock
M T
MT
Gonzalez
A M
AM
Surratt
C K
CK
Uhl
G R
GR
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins; D015870:Gene Expression; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000378:metabolism; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493216:Slc6a3 protein, rat; D014446:Tyrosine 3-Monooxygenase; D003913:Dextroamphetamine; D004298:Dopamine