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Published on: January 22, 2016
Chronic methamphetamine administration inhibits cerebral ischemia-induced hyperactivity in Mongolian gerbils
H Araki1, T Yamamoto, K Futagami
1Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan. haraki@md.okayama-u.ac.jp
Abstract:
The effect of single and chronic methamphetamine (MAP) administration on ischemia-induced hyperactivity was investigated and the mechanism of ischemia-induced hyperactivity was discussed. Ischemia-induced hyperactivity was recognized 3 h after ischemia. However, ischemia-induced hyperactivity at 1 day after ischemia was inhibited when MAP, in a dose of 10 mg/kg, was administered for 7 days and withdrawn for 7 days. It was reported that MAP treatment caused an irreversible decrease in the number of dopamine (DA) uptake sites. In addition to this, monoamine oxidase and the uptake of DA into the nerve terminals are disturbed by cerebral ischemia. Therefore, a lot of DA release happened during and immediately after ischemia, and a marked down-regulation of DA receptor occurred 24 h after ischemia in MAP-injected group. It is conceivable that the DA receptor, especially the presynaptic DA uptake site, is related to the occurrence of ischemia-induced hyperactivity. Further studies appear to be necessary to clarify acceptor susceptibility when neurotransmitters are normalized after transient ischemia.
Insights
Chronic methamphetamine (MAP) administration can inhibit ischemia-induced hyperactivity. This suggests dopamine (DA) pathways, particularly DA uptake sites, are crucial in understanding hyperactivity after cerebral ischemia.
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Cerebral ischemia can induce hyperactivity.
- Methamphetamine (MAP) affects dopamine (DA) systems.
- The interplay between MAP, ischemia, and hyperactivity requires elucidation.
Purpose of the Study:
- To investigate the effects of single and chronic MAP administration on ischemia-induced hyperactivity.
- To explore the underlying mechanisms of ischemia-induced hyperactivity in the context of MAP exposure.
Main Methods:
- Administration of methamphetamine (MAP) in specific doses (10 mg/kg) chronically (7 days) and acutely.
- Induction of cerebral ischemia.
- Observation and measurement of hyperactivity at different time points post-ischemia (3 hours, 1 day).
- Assessment of dopamine (DA) uptake sites and DA receptor regulation.
Main Results:
- Ischemia-induced hyperactivity was observed 3 hours after ischemia.
- Chronic MAP administration (10 mg/kg for 7 days, followed by 7 days withdrawal) inhibited hyperactivity at 1 day post-ischemia.
- MAP treatment led to a decrease in DA uptake sites.
- Cerebral ischemia disrupted monoamine oxidase and DA uptake, leading to increased DA release and DA receptor downregulation in MAP-treated groups.
Conclusions:
- Presynaptic dopamine (DA) uptake sites are implicated in ischemia-induced hyperactivity.
- The dopamine system, particularly DA uptake sites, plays a significant role in the observed hyperactivity following transient cerebral ischemia.
- Further research is needed to understand neurotransmitter normalization and receptor susceptibility after ischemia.
