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Co-administration of betulinic acid and methamphetamine causes toxicity to dopaminergic and serotonergic nerve terminals in the striatum of late adolescent rats.
- Source :
-
Journal of neurochemistry [J Neurochem] 2014 Mar; Vol. 128 (5), pp. 764-75. Date of Electronic Publication: 2013 Dec 03. - Publication Year :
- 2014
-
Abstract
- Psychostimulant methamphetamine (METH) is toxic to striatal dopaminergic and serotonergic nerve terminals in adult, but not in the adolescent, brain. Betulinic acid (BA) and its derivatives are promising anti-HIV agents with some toxic properties. Many METH users, particularly young men, are HIV-positive; therefore, they might be treated with BA or its derivative for HIV infection. It is not known whether BA, or any of its derivatives, are neurotoxic in combination with METH in the adolescent brain. The present study investigated the effects of BA and binge METH in the striatum of late adolescent rats. BA or METH alone did not decrease the levels of dopaminergic or serotonergic markers in the striatum whereas BA and METH together decreased these markers in a BA dose-dependent manner. BA+METH also caused decreases in the levels of mitochondrial complex I in the same manner; BA alone only slightly decreased the levels of this enzyme in striatal synaptosomes. BA or METH alone increased cytochrome c. METH alone decreased parkin, increased complex II and striatal BA levels. These results suggest that METH in combination with BA can be neurotoxic to striatal dopaminergic and serotonergic nerve terminals in the late adolescent brain via mitochondrial dysfunction and parkin deficit. We report a synergistic neurotoxicity of betulinic acid (BA) and methamphetamine (METH) to monoaminergic terminals in the striatum of male late adolescent rats. BA contribution to the neurotoxicity is decreasing mitochondrial complex I whereas METH contribution is decreasing parkin and increasing brain concentration of BA. We propose that clinical use of BA in young male METH users can be neurotoxic.<br /> (© 2013 International Society for Neurochemistry.)
- Subjects :
- Animals
Blotting, Western
Brain Chemistry drug effects
Caspase 3 metabolism
Chymotrypsin metabolism
Cytochromes c metabolism
Dose-Response Relationship, Drug
Electron Transport Complex I drug effects
Electron Transport Complex I metabolism
Electron Transport Complex II drug effects
Electron Transport Complex II metabolism
Fever chemically induced
Fever physiopathology
Male
Mitochondria drug effects
Mitochondria pathology
Neostriatum drug effects
Pentacyclic Triterpenes
Rats
Rats, Sprague-Dawley
Synaptosomes drug effects
Synaptosomes pathology
Ubiquitin-Protein Ligases metabolism
Betulinic Acid
Anti-HIV Agents toxicity
Dopamine Agents toxicity
Dopaminergic Neurons drug effects
Methamphetamine toxicity
Neostriatum pathology
Nerve Endings drug effects
Serotonergic Neurons drug effects
Triterpenes toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 128
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24151877
- Full Text :
- https://doi.org/10.1111/jnc.12496