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Published on: January 22, 2016
Methamphetamine Exposure During Development Causes Lasting Changes to Mesolimbic Dopamine Signaling in Mice
Daniel J Torres1,2, Jordan T Yorgason3, Marilou A Andres4
1Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, 96813, USA. djtorr@hawaii.edu.
Abstract:
Methamphetamine (MA) abuse remains a public health issue. Prenatal MA exposure (PME) poses a significant health problem, as we know very little about the drug's long-term physiological impact on the developing human brain. We investigated the long-term consequences of early MA exposure using a mouse model that targets the brain growth spurt, which occurs during human third-trimester. Adult mice previously subjected to acute MA during post-natal days 4-9 exhibited hyperactivity during the Open-Field Test, while exhibiting no motor coordination changes during the Rotarod Test. Neonatal MA exposure reduced basal dopamine (DA) uptake rates in adult nucleus accumbens slices compared with saline-injected controls. Although slices from neonatal MA-exposed mice showed no change in evoked DA signals in the presence of MA, they exhibited potentiated non-evoked DA release through DA efflux in response to MA. These data suggest that developmental MA exposure alters brain development to produce long-lasting physiological changes to the adult mesolimbic DA system, as well as altering responses to acute MA exposure in adulthood. This study provides new insights into an important, under-investigated area in drugs of abuse research.
Insights
Early methamphetamine exposure in mice causes lasting changes to the brain's dopamine system. This developmental exposure leads to hyperactivity and altered dopamine release in adulthood.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Methamphetamine (MA) abuse is a significant public health concern.
- The long-term physiological effects of prenatal MA exposure (PME) on the developing brain are not well understood.
Purpose of the Study:
- To investigate the long-term consequences of early MA exposure on brain development and function.
- To utilize a mouse model mimicking human third-trimester brain growth spurt.
Main Methods:
- Administered acute MA to mice during post-natal days 4-9.
- Assessed adult mice using Open-Field and Rotarod tests for behavioral changes.
- Measured dopamine (DA) uptake and release in nucleus accumbens slices from exposed and control mice.
Main Results:
- Adult mice exposed to MA neonatally showed hyperactivity but no motor coordination deficits.
- Neonatal MA exposure reduced basal dopamine uptake rates in adult nucleus accumbens.
- Exposed mice exhibited potentiated non-evoked DA release via DA efflux in response to MA.
Conclusions:
- Developmental MA exposure induces persistent physiological alterations in the adult mesolimbic dopamine system.
- These changes impact adult responses to acute MA exposure.
- Findings offer crucial insights into the under-researched area of drug abuse effects on brain development.
