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Acute methamphetamine administration upregulates NGFI-B mRNA expression in the striatum: co-localization with c-Fos
Cristina Bäckman1, Marisela Morales
1Cellular Neurophysiology, NIDA/NIH, Baltimore, Maryland 21224, USA. cbackman@intra.nida.nih.gov
Abstract:
In this study, the effects of acute methamphetamine administration on expression of the nuclear transcription factor NGFI-B mRNA and its co-localization with c-Fos immunoreactivity in the striatum were evaluated in animals receiving a single dose of methamphetamine (4 mg/kg) given at 2 or 6 h prior to perfusion. All animals received a daily saline injection for 6 days prior to methamphetamine treatment. We have found that, similar to c-fos activation, NGFI-B mRNA levels were significantly increased 2 h after methamphetamine treatment and returned to basal levels 6 h later. Induction of NGFI-B mRNA levels by methamphetamine was highest in central striatum as compared to the dorsomedial distribution pattern observed in control animals. After acute methamphetamine treatment, the distribution pattern of NGFI-B mRNA upregulation was very similar to that of methamphetamine induced c-Fos immunoreactivity. However, co-localization studies with c-Fos immunoreactivity showed that not all NGFI-B-positive cells contained c-Fos after methamphetamine treatment. Forty-five percent of all NGFI-B mRNA expressing neurons contained c-Fos immunoreactivity in the dorsomedial striatum as compared to 60% in central and 35% in ventrolateral striatum. This study provides a detailed description of the differential spatial and temporal modulation of NGFI-B and c-Fos expression in the striatum by acute methamphetamine treatment over time.
Insights
Acute methamphetamine increases NGFI-B mRNA and c-Fos expression in the striatum, with varying co-localization patterns over time. This reveals differential modulation of these key factors following drug exposure.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Methamphetamine (MA) is a psychostimulant with known effects on gene expression.
- Nuclear transcription factors like NGFI-B and c-Fos are crucial in neuronal responses to stimuli.
- The striatum is a key brain region involved in reward and motor control, significantly impacted by MA.
Purpose of the Study:
- To investigate the temporal and spatial effects of acute methamphetamine on NGFI-B mRNA expression.
- To examine the co-localization of NGFI-B mRNA with c-Fos immunoreactivity in the striatum after MA administration.
- To understand the differential modulation of NGFI-B and c-Fos by acute MA treatment.
Main Methods:
- Animal model receiving a single dose of methamphetamine (4 mg/kg) at 2 or 6 hours pre-perfusion.
- Daily saline injections for 6 days prior to MA treatment to control for handling effects.
- Quantitative analysis of NGFI-B mRNA levels and c-Fos immunoreactivity using in situ hybridization and immunohistochemistry.
Main Results:
- Methamphetamine significantly increased NGFI-B mRNA levels at 2 hours post-administration, returning to basal levels by 6 hours.
- NGFI-B mRNA induction was highest in the central striatum, differing from the dorsomedial pattern in controls.
- Co-localization studies revealed that while NGFI-B and c-Fos expression patterns were similar, not all NGFI-B-positive cells contained c-Fos, with varying percentages across striatal subregions.
Conclusions:
- Acute methamphetamine differentially modulates NGFI-B mRNA and c-Fos expression in a time- and region-specific manner within the striatum.
- The findings highlight the complex interplay between NGFI-B and c-Fos in the striatal response to acute stimulant exposure.
- This study provides detailed insights into the neurobiological mechanisms underlying methamphetamine's effects on immediate early gene expression.