Effect of methamphetamine self-administration on tyrosine hydroxylase and dopamine transporter levels in mesolimbic and nigrostriatal dopamine pathways of the rat.
OBJECTIVE
Many studies have examined the effect of experimenter-delivered methamphetamine on the mesolimbic and nigrostriatal dopamine pathways. In contrast, little is known about the effect of methamphetamine self-administration on these neuronal pathways. We studied the effect of methamphetamine self-administration on two key regulators of dopamine transmission, tyrosine hydroxylase (TH), and dopamine transporter (DAT), in components of the mesolimbic and nigrostriatal dopamine pathways.


METHODS
Rats self-administered methamphetamine (0.1 mg/kg per infusion, fixed-ratio-1 reinforcement schedule) or saline (control condition) for 9 h/day over 10 days. The brains of these rats were collected after 1 or 30 days of forced abstinence and the expression levels of TH and DAT were assayed by in situ, hybridization and western blot.


RESULTS
TH mRNA and protein levels were increased in the ventral tegmental area (VTA, the cell body region of the mesolimbic dopamine system) and the substantia nigra pars compacta (SNC, the cell body region of the nigrostriatal dopamine system) after 1 day, but not 30 days, of forced abstinence from methamphetamine. In contrast, methamphetamine self-administration had no effect on TH protein levels in dopaminergic terminals located in the nucleus accumbens and caudate-putamen. In addition, methamphetamine self-administration had no effect on DAT mRNA levels in the VTA.


CONCLUSIONS
Results suggest that extended daily access to self-administered methamphetamine results in a transient, short-lasting effect on mesolimbic and nigrostriatal dopamine neurons of the rat brain.
Cellular Neurobiology Research Branch, IRP/NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Jack D
JD
Shepard
David T
DT
Chuang
Yavin
Y
Shaham
Marisela
M
Morales
D000818:Animals; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000523:psychology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine