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Sex-specific effects of prenatal methamphetamine exposure on activity and blood pressure in aged offspring
A'Kaychia T Lowery1, Isaac G Johnson2, Anna G Mitchell2
1Graduate Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, United States.
Insights
Prenatal methamphetamine exposure in rats impacts adult offspring cardiovascular health and behavior. Female offspring showed increased baseline blood pressure and altered methamphetamine sensitivity, suggesting long-term effects.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Developmental Toxicology
Background:
- Prenatal methamphetamine exposure is a significant global health concern.
- Limited data exists on the long-term cardiovascular and behavioral consequences in adult offspring.
Purpose of the Study:
- To investigate the effects of prenatal methamphetamine exposure on methamphetamine sensitivity and cardiovascular function in aged rat offspring.
- To compare these effects between male and female offspring and control groups.
Main Methods:
- Pregnant rats self-administered methamphetamine intravenously, with offspring assessed for locomotor activity and cardiovascular function at aged stages.
- Blood pressure and angiotensin II-induced hypertension were measured non-invasively.
- Methamphetamine sensitivity was evaluated through dose-dependent locomotor activity assessments.
Main Results:
- Methamphetamine exposure increased locomotor activity in offspring, with reduced stereotypic responses at higher doses.
- Methamphetamine-exposed offspring exhibited resistance to angiotensin II-induced hypertension.
- Female offspring showed a tendency towards baseline hypertension and reduced hyperactivity at specific doses, unlike males.
Conclusions:
- Aged female offspring are particularly susceptible to prenatal methamphetamine exposure's effects on blood pressure and drug sensitivity.
- These findings highlight potential sex-specific long-term health risks associated with prenatal drug exposure.
Introduction:
Methamphetamine use during pregnancy is a global health issue, and there is limited knowledge on the cardiovascular and behavioral effects of prenatal methamphetamine exposure in adults. This study investigated how prenatal methamphetamine exposure in rats, via maternal intravenous self-administration, affected methamphetamine sensitivity and cardiovascular function in aged offspring compared to controls.
Methods:
The aged offspring were generated from dams either self-administering methamphetamine daily under extended-access conditions before and throughout pregnancy, or their respective sham control dams. Spontaneous and methamphetamine-induced locomotor activity was assessed in male and female offspring of both exposure groups after a range of methamphetamine doses at age 15-17 months. Cardiovascular function was assessed in male and female offspring aged 18-20 months of both groups.
Results:
Baseline blood pressure and angiotensin II (AngII)-induced hypertension were determined non-invasively via tail cuff measurements. Methamphetamine dose-dependently increased locomotor activity compared to baseline activity in both sexes and both exposure groups. In both sexes, AngII did not increase diastolic or systolic blood pressure in methamphetamine-exposed offspring, yet induced hypertension in controls. Methamphetamine administration induced dose-dependent hyperactivity in both exposure groups, with methamphetamine-exposed offspring showing resistance to stereotypic effects and thus increased activity at 3.2 mg/kg compared to controls. Notably, methamphetamine-exposed female offspring had a tendency to hypertension at baseline, driven by higher diastolic blood pressure, and showed reduced hyperactivity compared to controls at 1.0 mg/kg. Males did not exhibit these changes.
Conclusion:
These findings suggest that aged female offspring are particularly sensitive to the impacts of prenatal methamphetamine exposure on blood pressure and methamphetamine sensitivity.
