Methamphetamine-induced rapid decrease in dopamine transporter function: role of dopamine and hyperthermia.

Abstract

Single and multiple high-dose administrations of methamphetamine (METH) differentially decrease dopamine (DA) transporter (DAT) function, as assessed by measuring [(3)H]DA uptake into rat striatal synaptosomes prepared 1 h after treatment. Prevention of METH-induced hyperthermia attenuated the decrease in DAT activity induced by multiple injections of the stimulant. Likewise, this decrease was attenuated by previous depletion of striatal DA levels using alpha-methyl-p-tyrosine (alphaMT) or pretreatment with the D1 and D2 antagonists SCH-23390 and eticlopride, respectively. However, METH-induced hyperthermia was also blocked by alphaMT and eticlopride. Reinstatement of hyperthermia to alphaMT- or eticlopride-pretreated rats partially restored the METH-induced decrease in DAT activity. In contrast, neither prevention of METH-induced hyperthermia depletion of DA, nor DA antagonists altered the decrease in DAT function induced by a single administration of METH. Pretreatment with the antioxidant N-t-butyl-alpha-phenylnitrone prevented part of the decrease in DAT function associated with multiple, but not a single, METH injections. Although not tested directly, additional data presented here suggest that the reduction in DAT activity induced by a single METH administration constitutes a part of the total reduction observed immediately after multiple administrations. Taken together, the results indicate that DA, hyperthermia, and oxygen radicals contribute to a component of the rapid decrease in DAT function induced by multiple injections of METH but do not appear to be associated with the reduction induced by a single administration of the stimulant.

• Authors: R R Metzger, H M Haughey, D G Wilkins, J W Gibb, G R Hanson, A E Fleckenstein
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 295 Issue 3 Pg. 1077-85 (Dec 2000) ISSN: 0022-3565 [Print] United States
• PMID: 11082443 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Dopamine Plasma Membrane Transport Proteins
• Membrane Glycoproteins
• Membrane Transport Proteins
• Nerve Tissue Proteins
• Reactive Oxygen Species
• Receptors, N-Methyl-D-Aspartate
• Slc6a3 protein, rat
• Serotonin
• Methamphetamine
• Dopamine

Topics

• Animals
• Carrier Proteins (drug effects, physiology)
• Dopamine (physiology)
• Dopamine Plasma Membrane Transport Proteins
• Fever (physiopathology)
• Male
• Membrane Glycoproteins
• Membrane Transport Proteins
• Methamphetamine (pharmacology)
• Nerve Tissue Proteins
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species
• Receptors, N-Methyl-D-Aspartate (physiology)
• Serotonin (physiology)