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Persistence of tolerance to methamphetamine-induced monoamine deficits.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2007 Mar 15; Vol. 559 (1), pp. 46-54. Date of Electronic Publication: 2006 Dec 01. - Publication Year :
- 2007
-
Abstract
- Methamphetamine is a highly addictive and potent stimulant, the use of which has increased significantly in recent years. In addition to the severe behavioral and societal consequences associated with methamphetamine abuse, methamphetamine can cause persistent damage to monoaminergic nerve terminals in rats, as measured by either monoamine concentrations or activity of the rate limiting synthetic enzymes, tyrosine hydroxylase and tryptophan hydroxylase. Repeated, sub-neurotoxic doses of methamphetamine, however, can cause rats to become resistant to the neurotoxic effects of multiple high-dose administrations of methamphetamine; a phenomenon known as tolerance. This study investigates the persistence of tolerance evoked by pretreatment with escalating-dose administrations of methamphetamine. Rats were pretreated over several days with low, escalating doses of methamphetamine, followed by high-dose methamphetamine challenge after variable recovery periods. Results revealed that tolerance to monoaminergic deficits persisted for at least one week, but was completely eliminated by 31 days. There were no differences in the distribution of methamphetamine or its major metabolite, amphetamine, between methamphetamine-pretreated animals and saline-pretreated animals 2 h after the final methamphetamine challenge injection, and there were no regional differences in methamphetamine concentrations between the frontal cortex, hippocampus or striatum. We also observed that while methamphetamine pretreatment attenuated the hyperthermia caused by the high-dose methamphetamine challenge, significant reductions in methamphetamine-induced hyperthermia were not required for the development of tolerance with this regimen.
- Subjects :
- Amphetamines metabolism
Animals
Body Temperature drug effects
Central Nervous System Stimulants pharmacokinetics
Chromatography, Liquid
Dose-Response Relationship, Drug
Drug Tolerance
Male
Mass Spectrometry
Methamphetamine pharmacokinetics
Nerve Tissue Proteins metabolism
Rats
Rats, Sprague-Dawley
Biogenic Monoamines metabolism
Brain Chemistry drug effects
Central Nervous System Stimulants pharmacology
Methamphetamine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 559
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17239369
- Full Text :
- https://doi.org/10.1016/j.ejphar.2006.11.045